RNA Biol [JOURNAL]
Sun
200 papers
Developing the risk prediction model (ProlncSig) from lipoxygenase pathway-related lncRNAs for prognosis prediction in breast cancer.
Fu X, Wang W, Downs BM … +1 more , Li J
RNA Biol · 2025 Dec · PMID 40820368 · Full text
Alterations in cellular metabolism are known to play a crucial role in the development and progression of cancer. The lipoxygenase pathway, which controls unsaturated fatty acid metabolism, has been shown to regulate tum...
Alterations in cellular metabolism are known to play a crucial role in the development and progression of cancer. The lipoxygenase pathway, which controls unsaturated fatty acid metabolism, has been shown to regulate tumour progression and is commonly altered in breast cancer. In this study, we first obtained 11 lipoxygenase pathway genes from the Molecular Signatures Database (MSigDB). We then explored the lipoxygenase pathway-related long non-coding RNAs (lncRNAs) in breast cancer tissues from The Cancer Genome Atlas (TCGA) database. Information from our analysis was used to construct a risk prediction model (ProlncSig) to predict breast cancer prognosis. We found that ProlncSig could accurately identify breast cancer patients that had significantly shorter overall survival from those that had longer overall survival. Moreover, ProlncSig performs better in predicting prognosis than the clinicopathological features. Furthermore, GO and KEGG enrichment analysis showed that ProlncSig risk score had a high correlation with immune signature. We developed and validated an accurate prognostic risk prediction model (ProlncSig) based on lipoxygenase pathway-related lncRNAs, which has strong potential to provide prognostic information and may provide novel guidance for immunotherapeutic strategies for breast cancer patients.
Mechanistic insight into the pseudouridylation of RNA.
Lin TY, Stone Y, Glatt S
RNA Biol · 2025 Dec · PMID 40781894 · Full text
Pseudouridylation (Ψ) is a highly abundant and conserved RNA modification that is present in all three domains of life. The incorporation of Ψ can affect the stability of RNAs, modulate their interaction patterns, and re...
Pseudouridylation (Ψ) is a highly abundant and conserved RNA modification that is present in all three domains of life. The incorporation of Ψ can affect the stability of RNAs, modulate their interaction patterns, and regulate many other aspects of RNA biology. Ψ are introduced by a structurally highly related enzyme family, called pseudouridine synthases (PUS). Each PUS enzyme targets distinct RNA substrates and target sites. Dysregulation of PUS enzymes has been implicated in neurodevelopmental disorders, mitochondrial diseases and cancer. These clinical consequences highlight the ultimate need to understand how these enzymes catalyze their modification reactions and achieve target selectivity as well as specificity. In this review, we summarize the currently available structural information on PUS enzymes and highlight the most recent progress in understanding some underlying mechanistic principles. Furthermore, we illustrate the increasing therapeutic applications related to the so-called 5 RNA base.
Dynamic shifts in isomiR profiles during parasite maturation of .
Sais D, Chowdhury S, Nguyen PT … +6 more , Cwiklinski K, Nguyen TD, Nguyen TA, Dalton J, Donnelly S, Tran N
RNA Biol · 2025 Dec · PMID 40745916 · Full text
We investigated the isomiR profiles of the parasitic worm across three developmental stages: newly excysted juveniles (NEJ), juveniles (JUV), and adults. Our analysis revealed a distinct shift in isomiR distribution dur...
We investigated the isomiR profiles of the parasitic worm across three developmental stages: newly excysted juveniles (NEJ), juveniles (JUV), and adults. Our analysis revealed a distinct shift in isomiR distribution during maturation, with NEJs exhibiting a higher abundance and diversity of isomiRs compared to later stages. Notably, isomiRs were often the dominant miRNA form in NEJs, whereas a transition to canonical miRNAs occurred as the parasite matured. This temporal variation suggests that isomiR expression may be linked to the parasite's life cycle. We observed that truncated isomiRs were more prevalent, with uracil additions at the 3'end and adenosine at the 5' end being most common. At least 10% of the miRNA population consisted of 5' end isomiRs, which have the potential to redirect target interactions towards metabolic and developmental pathways. Furthermore, we show that the cleavage sites in primary miRNAs are similar to those found in mammalian cells, and Dicer-mediated cleavage appears to play a significant role in isomiR generation. We believe that the diversification of miRNA sequences through isomiR production is an evolutionary adaptation that enhances the parasite's ability to tune gene expression during infection and development. This regulatory plasticity may facilitate successful infection and long-term persistence within diverse mammalian hosts. Understanding the roles of isomiRs in parasitic worms could provide new insights into parasite biology and identify potential targets for controlling parasitic infections.
Impact of Gemin5 in protein synthesis: phosphoresidues of the dimerization domain regulate ribosome binding.
Abellan S, Escos A, Francisco-Velilla R … +1 more , Martinez-Salas E
RNA Biol · 2025 Dec · PMID 40734649 · Full text
RNA-binding proteins are involved in all steps of gene expression. Their malfunction has important consequences for cell growth through dysregulation of protein synthesis events leading to cancer. Gemin5 is a predominant...
RNA-binding proteins are involved in all steps of gene expression. Their malfunction has important consequences for cell growth through dysregulation of protein synthesis events leading to cancer. Gemin5 is a predominantly cytoplasmic protein involved in spliceosome assembly and gene expression reprogramming. The protein is phosphorylated at multiple sites, although the role of the individual phosphorylated residues remains poorly understood. With the aim to understand the impact of Gemin5 post-translation modifications for RNA-binding, protein synthesis, and therefore cell growth, we have analysed the role of conserved P-residues located in the dimerization domain of the protein in subcellular localization, protein stability, interactome, ribosome binding and translation regulation. We show that the activation of signalling pathways in response to a dsRNA mimic, which leads to phosphorylation of eIF2α, enhanced the intensity of Gemin5 binding to a cognate RNA ligand. In addition, ribosome binding decreased when Ser/Thr 847 and 852-854 are substituted by a non-phosphorylatable residue, consistent with decreased protein stability, and reduced number of associated factors. Similar analyses of phosphomimetic mutants (S847D and STS852-854DDD) suggested conformational changes of the protein structure as the responsible factor for the defective proteins. Moreover, cap-dependent protein synthesis was significantly altered by the triple substitution STS/DDD, pointing towards a role of these residues in protein synthesis regulation.
Carrot and stick: how RNase R contributes to function and destruction of the translation machinery.
Paternoga H, Dimitrova-Paternoga L
RNA Biol · 2025 Dec · PMID 40734258 · Full text
RNA is fundamental for life, and its homoeostasis is a critical contributor to cellular growth and adaptation to stress. Key RNA species include messenger RNA (mRNA) and non-coding RNAs, such as transfer RNA (tRNA), or r...
RNA is fundamental for life, and its homoeostasis is a critical contributor to cellular growth and adaptation to stress. Key RNA species include messenger RNA (mRNA) and non-coding RNAs, such as transfer RNA (tRNA), or ribosomal RNA (rRNA), that are essential for ribosome formation and translation of the genetic code. Furthermore, various other non-coding RNAs are expressed at each growth stage. Given RNA's abundance and its role in all cellular processes, RNases - enzymes responsible for RNA degradation and processing - are central to RNA metabolism. In this review, we discuss the pivotal contribution of the 3' exonuclease RNase R to bacterial RNA homoeostasis. We focus on its functions in regulating and degrading components of the translation machinery, including the trans-translation system, and we take a look at recent structural studies that shed new light on the activities of this important enzyme.
Derailing the host machinery to achieve replication: how viroid and viroid-like RNAs successfully copy their genomes in hostile territory.
Kalantidis K, Tselika M, Kallemi P … +3 more , Bardani E, Kryovrysanaki N, Katsarou K
RNA Biol · 2025 Dec · PMID 40720211 · Full text
Circular infectious RNAs have been known for several decades. Their biology has been intriguing from the beginning, partly due to the antithesis between their efficiency and tiny size. Amongst infectious circular RNAs vi...
Circular infectious RNAs have been known for several decades. Their biology has been intriguing from the beginning, partly due to the antithesis between their efficiency and tiny size. Amongst infectious circular RNAs viroids hold a special place not only because they were the first to be characterized as such but also because they have been extensively studied as a group. Viroids do not encode proteins and therefore have to rely for their biological cycle on the host factors. As a result, the identification and functional characterization of host factors enabling their biological cycle has been of prime importance to the community. With the advent of high throughput sequencing technologies, viroid-like infectious RNAs have been found in plants, fungi, and animals, including mammals, making understanding their biology even more interesting and important. In this review, we summarize what is known about the replication of these tiny yet very efficient infectious RNAs.
C-terminal tagging impairs AGO2 function.
Shah KM, Crozier AFF, Assaraf A … +5 more , Arya M, Grevitt P, Mardakheh F, Plevin MJ, Sharp TV
RNA Biol · 2025 Dec · PMID 40698645 · Full text
MicroRNA-mediated gene silencing is a conserved mechanism of post-transcriptional gene regulation across metazoans. It depends on base pairing between small RNAs and mRNAs, and on protein complexes including the RNA-indu...
MicroRNA-mediated gene silencing is a conserved mechanism of post-transcriptional gene regulation across metazoans. It depends on base pairing between small RNAs and mRNAs, and on protein complexes including the RNA-induced silencing complex (RISC), where Argonaute 2 (AGO2) plays a central role. A full understanding of RNA silencing requires reliable molecular tools to study AGO2 and RISC. Affinity tagging and antibody-based methods can introduce artefacts, and both the - and C-terminal domains of AGO2 are critical for its function. While N-terminal tags are frequently used, and a recent study in mice showed altered activity in N-terminal HaloTag-AGO2 fusions, the consequences of C-terminal tagging remain underexplored. CRISPaint, a CRISPR-Cas9-based technique, enables endogenous C-terminal tag fusions without requiring homology arms. Using this system, we generated the first C-terminal HaloTag fusion of AGO2 (AGO2HALO) in human A549 cells. We found that the AGO2HALO fusion protein exhibits reduced binding with TNRC6A, with no effect on cell viability. However, it significantly impairs RNA cleavage, silencing activity, and nuclear localization. We further compared AGO2-EGFP and EGFP-AGO2 using transient transfection. N-terminally tagged AGO2 retained wild-type-like function and localization, while C-terminally tagged AGO2 was impaired in siRNA and miRNA silencing, nuclear import, and P-body localization. These results demonstrate that a C-terminal HaloTag compromises AGO2 functionality and is unsuitable for studying RISC biology. Our findings highlight the importance of validating tagging strategies to avoid misleading conclusions due to tag-induced functional defects. Pre-print, bioRxiv.
The hidden power of antisense long non-coding RNAs: a dive into a novel regulatory layer mediated by double-stranded RNA formation.
Lamping JP, Krebber H
RNA Biol · 2025 Dec · PMID 40629869 · Full text
Over the past decade, non-coding RNAs (ncRNAs) have gained prominence in research due to their widespread presence in cells, yet their functions remain increasingly complex and less understood. Despite being initially de...
Over the past decade, non-coding RNAs (ncRNAs) have gained prominence in research due to their widespread presence in cells, yet their functions remain increasingly complex and less understood. Despite being initially deemed 'junk', many lncRNAs are now recognized as key regulators in cells and are often affected in disease contexts. Notably, numerous mRNAs have annotated antisense RNAs (asRNAs). Because asRNAs resemble the largest group of lncRNAs and were identified to serve a general function in , they are the focus of this review. In , the absence of RNA interference (RNAi) enables unbiased study and allowed researchers to investigate their roles in gene regulation more directly with intriguing results, summarized here. Expression of asRNA leads to the formation of double-stranded RNAs (dsRNAs) with the regarding sense counterpart, resulting in enhanced gene expression through preferential nuclear export. Thus, these hidden leaders can boost gene expression and require future attention pivotal for elucidating their influence on biological processes and revealing disease mechanisms.
The secret life of RNA and lipids.
Czerniak T, Saenz JP
RNA Biol · 2025 Dec · PMID 40613519 · Full text
There is no life without RNA or lipids. But could there be life with only RNA and lipids? The discovery that RNA can catalyse reactions in addition to encoding information opened new directions for engineering life and t...
There is no life without RNA or lipids. But could there be life with only RNA and lipids? The discovery that RNA can catalyse reactions in addition to encoding information opened new directions for engineering life and the possibility of life emerging from an RNA World. But a key missing ingredient for RNA-based biochemical systems is a mechanism to organize RNAs and regulate their activity. Lipids, which are essential for life and one of the most ancient biomolecules, can spontaneously self-assemble to form membranous bilayers, theoretically providing a surface that can serve to concentrate, protect, and regulate RNAs. This review explores the interactions between RNA and lipids, including the chemical basis for their interactions, and the implications for synthetic biology, RNA World, and modern cell biology. We discuss observations that RNA can selectively bind to lipid membranes in a sequence-dependent manner, and entertain how these interactions might be employed to engineer RNA-based sensors and regulatory elements in synthetic systems. The emerging field of RNA-lipid interactions opens new possibilities for engineering orthogonal biochemistries for synthetic cells, innovations in RNA therapeutics, and discovering potentially new facets of cellular regulation.
Fusion transcripts landscape in hepatocellular carcinoma and potential impact on the expression of fusion partners.
Öztemur Islakoğlu Y, Korhan P, Binokay L … +6 more , Keleş B, Bağırsakçı E, Uludağ Taşçıoğlu M, Şamdancı E, Karakülah G, Atabey N
RNA Biol · 2025 Dec · PMID 40613496 · Full text
Fusion transcripts (FTs) are RNA molecules, also known as chimeric transcripts, formed through chromosomal rearrangements or transcriptional processes, contributing to tumorigenesis. This study systematically examined tu...
Fusion transcripts (FTs) are RNA molecules, also known as chimeric transcripts, formed through chromosomal rearrangements or transcriptional processes, contributing to tumorigenesis. This study systematically examined tumour-specific FTs in hepatocellular carcinoma (HCC) using high-throughput RNA sequencing data from independent datasets and The Cancer Genome Atlas (TCGA). Our analysis included 328 HCC samples. Using STAR-Fusion, we identified 15 novel tumour-specific FTs, with SERPINA1-H19 as the most recurrent fusion event. Comparative expression analysis of fusion partner genes revealed significant downregulation in HCC tumours relative to normal adjacent liver tissues (NAT). We validated the expression levels of the key partner genes with 436 TCGA samples serving as an and in with 42 samples. ALB, APOA2, IGF2, MT2A, SERPINA1, and H19, which are key liver-associated genes, were frequently involved in tumour-specific fusion events suggesting either a loss of tumour suppressor property or gaining a novel function playing a role in hepatocarcinogenesis. Detailed characterization of SERPINA1-H19 identified 16 transcript variants with distinct structural modifications that may impact its functional output. Furthermore, low expression of SERPINA1 and H19 was associated with more aggressive HCC phenotypes. Overall, this study established a comprehensive repository of FTs for the first time, offering valuable insights into their role in HCC and their potential to serve as diagnostic and prognostic biomarkers for HCC.
Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease.
Zhang Y, Huang Z, Lu W … +1 more , Liu Z
RNA Biol · 2025 Dec · PMID 40613493 · Full text
Alternative polyadenylation (APA) is a critical post-transcriptional regulatory mechanism that generates diverse mRNA isoforms by selecting different polyadenylation sites within pre-mRNAs, thereby modulating the length...
Alternative polyadenylation (APA) is a critical post-transcriptional regulatory mechanism that generates diverse mRNA isoforms by selecting different polyadenylation sites within pre-mRNAs, thereby modulating the length of the 3' untranslated region (3' UTR), thereby fine-tuning gene expression and protein synthesis. APA regulation involves conserved cis-acting elements, trans-acting factors, and key protein complexes such as CPSF and CSTF, influenced by the cellular context and various RNA-binding proteins. To address the complexity of APA, comprehensive methodologies and computational tools have been developed, leading to extensive APA databases with detailed biological annotations. Recent advancements in high-throughput sequencing and single-cell technologies have enhanced our understanding of APA's dynamic regulation across tissues and developmental stages, revealing its significant impact on cellular heterogeneity and disease progression. APA plays essential roles in numerous physiological processes, including neuronal homoeostasis, immune regulation, cardiovascular and vascular development, myogenesis, and metabolism. Dysregulation of APA is associated with a wide range of diseases, including neurodegenerative disorders, autoimmune conditions, cardiovascular diseases, metabolic syndromes, and genetic disorders. Clinically, targeting APA regulatory mechanisms offers promising opportunities for therapeutic interventions and the development of personalized medical strategies. This review highlights the pivotal role of APA in gene regulation and disease, emphasizing the need for continued research to unravel its complex mechanisms and leverage its potential in advancing precision medicine.
Novel non-coding FOXP3 transcript isoform associated to potential transcriptional interference in human regulatory T cells.
Cases M, Ritter N, Rincon-Arevalo H … +13 more , Kroh S, Adam A, Kirchner M, Moradian H, Gossen M, Dzamukova M, Manukyan A, Landthaler M, Kressler C, Hauser AE, Depledge DP, Polansky JK, Chang HD
RNA Biol · 2025 Dec · PMID 40605177 · Full text
CD4+ regulatory T cells (T) are critical for immune tolerance and the transcription factor Forkhead Box P3 (FOXP3) plays a crucial role in their differentiation and function. Recently, an alternative promoter has been re...
CD4+ regulatory T cells (T) are critical for immune tolerance and the transcription factor Forkhead Box P3 (FOXP3) plays a crucial role in their differentiation and function. Recently, an alternative promoter has been reported for FOXP3, which is active only in T and could have profound implications for the output of the locus, and therefore, for the functionality of these cells. By direct RNA sequencing we identified multiple novel FOXP3 transcriptional products, including one relatively abundant isoform with an extended 5' UTR that we named 'longFOXP3'. Western blotting, analysis of public mass spectrometry data, and transfection of transcribed RNA suggested that longFOXP3 is not coding. Furthermore, we show using two distinct RNA single-molecule fluorescence in situ hybridization technologies that transcription from the upstream promoter correlates with decreased levels of FOXP3 at the mRNA and protein levels. Together, we provide compelling evidence that the transcriptional output of the human FOXP3 locus is far more complex than that of the current annotation and warrants a more detailed analysis to identify coding and non-coding transcript isoforms. Furthermore, the alternative promoter may interfere with the activity of the canonical promoter, evoking intragenic transcriptional interference, and in this way, fine-tune the levels of FOXP3 in human T.
SARS-CoV-2 RNA-binding protein suppresses extracellular miRNA release.
Mun H, Shin CH, Fei Q … +21 more , Giraldo AEL, Choi KM, Lee JW, Kim K, Min KW, Shi L, Bedford MT, Kim DC, Chun YL, Ryu S, Kim D, Chang JH, Westrope RT, Shay M, Nguyen E, Hur JK, Agyenda A, Kim NC, Kang SU, Lee W, Yoon JH
RNA Biol · 2025 Dec · PMID 40590376 · Full text
SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemi...
SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, Nsp9 inhibits extracellular release of let-7b and subsequent antiviral activity via TLR7. These results demonstrate that SARS-CoV-2 hijacks the host RNA metabolism to suppress antiviral responses and to shut down cellular transcription. Our findings of how a natural ligand of TLR7, miRNA let-7b, is suppressed by SARS-CoV-2 RBPs will advance our understanding of COVID-19 and SARS-CoV-2 therapeutics.
Identification and characterization of new structured RNA classes in plants.
Sack M, Reinhardt M, Burgardt R … +4 more , Berg P, Bauer J, Wachter A, Weinberg Z
RNA Biol · 2025 Dec · PMID 40587820 · Full text
Alternative splicing is a very important mechanism to diversify an organism's transcriptome with minimal increases in genome size. It can modify the function of the finished protein or affect its regulation, e.g. induce...
Alternative splicing is a very important mechanism to diversify an organism's transcriptome with minimal increases in genome size. It can modify the function of the finished protein or affect its regulation, e.g. induce nonsense-mediated decay (NMD) to degrade the transcript. Mechanisms that affect alternative splicing are therefore of great interest. It has been shown that splicing can be affected by RNA secondary structures within pre-mRNAs. These structured regions of RNA (strucRNA) would affect their transcript in , but only a few such cases are known in plants. In this study, we interrogate plant genomes for -regulatory strucRNAs. By applying a comparative-genomics-based approach to 130 plant genomes, we identified 16 strucRNA candidates. Five candidates likely regulate in using alternative splicing and NMD. Other predictions might not regulate alternative splicing, including four putative small nucleolar RNAs (snoRNAs). Of our five -regulatory strucRNAs that are implicated in alternative splicing control, two are now experimentally validated in follow-up studies. These results stand in contrast to the few previously validated examples. Although we were able to predict some strucRNAs, all motifs had generally modest levels of covariation, which is a pattern of mutations that indicates a conserved secondary structure. With few mutations, comparative-genomics-based approaches to find strucRNAs are less effective. Other approaches of finding regulatory RNAs in plants might thus be needed, and more available genomic or transcriptomic data might improve the quality and quantity of promising candidates.
Profile of tRNA-derived short non-coding RNAs during monocyte differentiation and their role in macrophage survival.
Jayaram A, Galande S, Sharbati S … +2 more , Deshpande D, Pawar K
RNA Biol · 2025 Dec · PMID 40575931 · Full text
Monocytes, a type of leukocytes, are key players in immune responses, transitioning to macrophages at infection sites. Differentiation, which is crucial for macrophage survival and resistance to apoptosis, is a tightly r...
Monocytes, a type of leukocytes, are key players in immune responses, transitioning to macrophages at infection sites. Differentiation, which is crucial for macrophage survival and resistance to apoptosis, is a tightly regulated process. Based on our earlier findings implicating the 5'-fragment of tRNA (5'-HisGUG) in macrophage biology, we specifically focused on these fragments to investigate its regulation during monocyte-to-macrophage differentiation and its role in macrophage survival. We performed small RNA sequencing during monocyte-to-macrophage differentiation using THP-1 cells and identified 5'-HisGUG as a prominently regulated tDR. Notably, transfection of 5'-HisGUG in macrophages decreased survival under apoptotic stress. We propose that 5'-HisGUG can also act as an obstructive RNA (oRNA), and its reduction is critical for macrophage survival under stress.
Molecular basis of backsplicing regulation and its application to manipulate circRNA levels.
Wang Y, Dzakah EE, Wang X
RNA Biol · 2025 Dec · PMID 40575920 · Full text
Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which have been implicated in both physiology and human diseases. Most circRNAs are typically generated through backsplicing, where a downstre...
Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which have been implicated in both physiology and human diseases. Most circRNAs are typically generated through backsplicing, where a downstream splice donor is covalently joined to an upstream splice acceptor. Backsplicing is dependent on the spliceosome machinery and is precisely controlled by various -elements and -factors. In the present review, we summarize the molecular mechanisms of backsplicing regulation as well as their physiological and pathological significance. Additionally, we discuss the strategies to manipulate circRNA expression and , aiming to explore the application of circRNA biogenesis in the diagnosis and therapy of human diseases.
Comprehensive analysis of tRNA-derived fragment expression in endometriosis using PANDORA-seq technology.
Huang J, Cheng J, Zhang D … +3 more , Wang Y, Liang H, Liu L
RNA Biol · 2025 Dec · PMID 40575905 · Full text
Endometriosis is a common gynaecological disease and there is no reliable non-invasive biomarker for its unknown pathogenesis. TRF is differentially expressed in a variety of cancers and is a new non-invasive biomarker....
Endometriosis is a common gynaecological disease and there is no reliable non-invasive biomarker for its unknown pathogenesis. TRF is differentially expressed in a variety of cancers and is a new non-invasive biomarker. The aim of this study was to reveal the full landscape of tRF expression profile in endometriosis using PANDORA-seq, which will provide strong target support for early diagnosis and treatment. PANDORA-seq was used to detect the eutopic and ectopic endometrial tissues of 4 patients with ovarian endometriosis and 4 normal endometrial tissues in the control group, and qRT-PCR was performed to verify. The target genes of DEtRF were predicted by TargetScan and miRanda, and the potential functions of differential tRFs were studied by bioinformatics such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), so as to further elucidate the pathogenesis of endometriosis. Under the screening conditions of |Fold Change| ≥ 2 and Padj < 0.05, a total of 13 common differentially expressed tRFs were identified when comparing the disease groups, defined as endometriosis-affected eutopic endometrial tissue (EU) and ectopic endometrial tissue (EC), with the control group consisting of eutopic endometrial tissue from normal uteri (EN). Eleven DEtRFs target genes were highly enriched in endometriosis-related signalling pathways, such as MAPK, Ras, p53 and mitophagy-related pathways. Differentially expressed tRF may be involved in the development of endometriosis by regulating target genes in MAPK and autophagy signalling pathways. DEtRF is expected to be a new non-invasive biomarker for endometriosis.
Biology and utilization of R2 retrotransposons.
Luo S, Chen Q, Chen Y … +1 more , Li W
RNA Biol · 2025 Dec · PMID 40566873 · Full text
R2 elements serve as a class of non-long terminal repeat (non-LTR) retrotransposons found in animal genomes that specifically insert into the ribosomal DNA (rDNA) sequences of host genomes. Each R2 element contains a sin...
R2 elements serve as a class of non-long terminal repeat (non-LTR) retrotransposons found in animal genomes that specifically insert into the ribosomal DNA (rDNA) sequences of host genomes. Each R2 element contains a single open reading frame (ORF) encoding a multifunctional protein with nucleic acid-binding, reverse transcriptase, and endonuclease activities, enabling specific genomic integration via a mechanism called target-primed reverse transcription (TPRT). As a classical model for studying retrotransposition mechanisms, R2 elements possess unique biological properties and precise integration capabilities, which have inspired novel genome engineering strategies. In this review, we summarize the components and integration mechanisms of R2 retrotransposons and highlight the recent advances in employing these mobile elements for targeted gene integration. Finally, we present future directions for the utilization of R2 retrotransposons as novel biotechnological tools.
Early posttranscriptional response to tetracycline exposure in a gram-negative soil bacterium reveals unexpected attenuation mechanism of a DUF1127 gene.
Kothe JAF, Sauerwein T, Dietz T … +6 more , Scheuer R, Elhossary M, Barth-Weber S, Wähling J, Förstner KU, Evguenieva-Hackenberg E
RNA Biol · 2025 Dec · PMID 40534149 · Full text
The gram-negative, soil-dwelling plant symbiont shares its free-living habitat with antibiotic producers. To learn about early steps of its adaptation to antibiotics, we analysed transcriptome changes after 10 min expos...
The gram-negative, soil-dwelling plant symbiont shares its free-living habitat with antibiotic producers. To learn about early steps of its adaptation to antibiotics, we analysed transcriptome changes after 10 min exposure to subinhibitory amount of tetracycline (Tc). RNA-seq revealed 297 differentially expressed genes. Besides ten upregulated ribosomal genes, there was no recognizable functional pattern in the observed changes. However, polar differential expression pattern was observed: Mostly, upregulated genes were first and downregulated genes downstream in operons. Furthermore, we detected mRNA stabilization upon Tc exposure for several up- and down-regulated genes. Thus, mRNA stabilization contributed to increased mRNA levels, but for downstream genes its effect was probably counteracted by premature transcriptional termination caused by disrupted coupling between transcription and translation. Using reporter constructs, we found that a DUF1127 gene, showing highest mRNA increase, is controlled by transcription attenuation depending on the translation of an upstream ORF (uORF). Our data suggest the following model: The attenuation strongly depends on the accessibility of C-rich codons at the beginning of the uORF. The accessibility is guaranteed by translation of the uORF, and is possible in a time window after a ribosome moves downstream and before a next ribosome occupies the ribosomal binding site (RBS). The accessibility is blocked either by impaired translation initiation or, in the absence of ribosome binding, by base-pairing between the RBS and the C-rich codons. We propose that this is used by bacteria to monitor ribosome availability and translation efficiency, and to ensure reciprocal expression of the DUF1127 gene.
Snhg12 targets miR-199a-5p to regulate osteogenic differentiation of TDSCs via the Fzd4/Wnt/β-catenin pathway.
Li X, Xu B, Wang Z … +3 more , Li M, Wu H, Chen B
RNA Biol · 2025 Dec · PMID 40503725 · Full text
Heterotopic ossification (HO) is the formation of bone tissue outside the normal skeletal structure following musculoskeletal injury. Long non-coding RNAs (lncRNAs) play a regulatory role in guiding stem cell differentia...
Heterotopic ossification (HO) is the formation of bone tissue outside the normal skeletal structure following musculoskeletal injury. Long non-coding RNAs (lncRNAs) play a regulatory role in guiding stem cell differentiation towards osteogenic lineages. Through lncRNA sequencing in this study, we observed an up-regulation of small nucleolar RNA host gene 12 (Snhg12) in HO tissues. The precise function of Snhg12 in the process of tendon stem cells (TDSCs) osteogenic differentiation remains uncertain. Our findings suggest that Snhg12 overexpression exacerbated HO, whereas its suppression ameliorated HO. The lncRNA Snhg12 directly targeted miR-199a-5p to alleviate the suppression of Fzd4 caused by miR-199a-5p. Functionally, experiments conducted in vitro and in vivo demonstrated that HO formation was inhibited by the down-regulation of Fzd4 through the up-regulation of miR-199a-5p. In rescue experiments conducted in vitro, the inhibition of miR-199a-5p or overexpression of Fzd4 reversed the improvement in HO caused by Snhg12 knockdown, and Fzd4 regulated the process of osteogenic differentiation in TDSCs by the Wnt/β-catenin pathway. Taken together, these results demonstrate that Snhg12 modulates HO formation via the Snhg12-miR-199a-5p-Fzd4/Wnt/β-catenin signalling pathway.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe