RNA Biol [JOURNAL]
Sun
200 papers
Bevacizumab induces apoptosis in glioblastoma cells by upregulating miR-4695-5p to inhibit PKMYT1.
Shen Y, Yang C, Wang H … +4 more , Hu S, Hao Y, Geng Y, Huang S
RNA Biol · 2026 Dec · PMID 42133791 · Full text
We sought to determine the pro-apoptotic effects of bevacizumab in glioblastoma (GBM) and to elucidate the contribution of the miR-4695-5p/PKMYT1 pathway to this process. Following treatment of U87MG and U251 GBM cells w...
We sought to determine the pro-apoptotic effects of bevacizumab in glioblastoma (GBM) and to elucidate the contribution of the miR-4695-5p/PKMYT1 pathway to this process. Following treatment of U87MG and U251 GBM cells with dose-gradient bevacizumab, cellular responses were evaluated by measuring apoptosis (flow cytometry) and proliferation (CCK-8), while RT-qPCR quantified changes in miR-4695-5p, Bax, and Bcl-2 expression. PKMYT1, bioinformatically predicted as a downstream target of miR-4695-5p, was verified via luciferase reporter assays. The functional link between miR-4695-5p and PKMYT1 was established using miRNA mimics and PKMYT1 overexpression rescue experiments. The critical role of this pathway in bevacizumab-induced apoptosis was ultimately confirmed by co-treating cells with bevacizumab and either a miR-4695-5p inhibitor or a PKMYT1 overexpression vector. Bevacizumab induced apoptosis in GBM cells U87MG and U251 in a dose-dependent manner. After bevacizumab treatment, the expression level of miR-4695-5p increased, and inhibiting miR-4695-5p expression reduced the pro-apoptotic effect of bevacizumab on U87MG and U251 cells. miR-4695-5p could target and inhibit PKMYT1 expression. Overexpression of PKMYT1 suppressed the pro-apoptotic effect of bevacizumab on U87MG and U251 cells, indicating that bevacizumab induces apoptosis in GBM cells by upregulating miR-4695-5p to target and inhibit PKMYT1. This study reveals the role and mechanism of bevacizumab in inducing apoptosis in GBM cells, namely by upregulating miR-4695-5p expression to target and inhibit the expression of the anti-apoptotic protein PKMYT1, thereby inducing apoptosis in GBM cells. This provides new directions and targets for research and treatment of gliomas.
The lncRNA ZNF295-AS1 alleviates lung squamous cell carcinoma progression by reducing miR-96-5p and inhibiting cancer cell invasiveness.
Huang Y, Yan D, Hao Z … +1 more , Ni X
RNA Biol · 2026 Dec · PMID 42132046 · Full text
Lung squamous cell carcinoma (LUSC) is highly invasive, and patients with advanced disease generally have a poor prognosis. ZNF295-AS1 is abnormally expressed in lung cancer. This study aims to investigate the prognostic...
Lung squamous cell carcinoma (LUSC) is highly invasive, and patients with advanced disease generally have a poor prognosis. ZNF295-AS1 is abnormally expressed in lung cancer. This study aims to investigate the prognostic value of ZNF295-AS1 in LUSC and its potential regulatory mechanisms. This study enrolled 116 patients with lung upper-segment carcinoma (LUSC) and obtained LUSC tissue and adjacent normal tissue during surgery. RT-qPCR was used to assess the expression levels of ZNF295-AS1 and miR-96-5p in tissues and cell lines. Cox proportional hazards analysis identified independent factors affecting LUSC prognosis. CCK-8 and Transwell assays assessed cellular proliferation, invasion, and migration capabilities, respectively. DLR validated the relationship between ZNF295-AS1 and miR-96-5p. Compared with normal tissue and BEAS-2B cells, ZNF295-AS1 is significantly downregulated in LUSC tissue and cells. ZNF295-AS1 negatively regulates miR-96-5p level by binding to it as a target. ZNF295-AS1 serves as a protective factor influencing LUSC prognosis. Furthermore, elevating ZNF295-AS1 levels reduces miR-96-5p expression in cells, thereby diminishing the proliferation, migration, and invasion capabilities of LUSC cell lines and mitigating LUSC progression. ZNF295-AS1 demonstrates significant prognostic value in clinical settings for LUSC and holds promise as a novel prognostic biomarker. ZNF295-AS1 acts as a protective factor against LUSC. Mechanistically, ZNF295-AS1 alleviates LUSC progression and improves patient prognosis by regulating miR-96-5p levels.
Evaluating -derived 3'end sequences for functional transgene expression in human cells using synthetic mRNA delivery.
Rosemann J, Jahr GT, Macho J … +2 more , Haemmerle M, Gutschner T
RNA Biol · 2026 Dec · PMID 42093635 · Full text
The poly(A) tail is a key structural element found in almost all mammalian messenger RNAs, required for stabilizing the transcript and enhancing translation. Here, we evaluate poly(A) replacement strategies based on sequ...
The poly(A) tail is a key structural element found in almost all mammalian messenger RNAs, required for stabilizing the transcript and enhancing translation. Here, we evaluate poly(A) replacement strategies based on sequence elements derived from the long non-coding RNA . undergoes RNase P processing to generate a 3' end protected by a conserved triple helix. Importantly, this triple helix structure was shown to enhance translation when placed downstream of an open reading frame. We compared -derived 3' end motifs with canonical poly(A) tails incorporated into a synthetic reporter RNA encoding a green fluorescent protein. Our results corroborate the central role of the poly(A) tail for efficient expression, showing that the tested -derived motifs can generally support translation of the reporter mRNA, although they consistently underperform compared to canonical poly(A) tails. Future work should optimize triplex sequence and folding to enhance translation capacity, test additional triplex structures, and explore small molecule to regulate stability and translation of triplex-containing RNAs for applications in synthetic biology and RNA-based therapeutics.
The mRNA architecture of the translation termination site primes programmed stop codon readthrough events in .
Kansara L, Wolfstetter G, Wintermayr D … +4 more , Alexopoulos I, Escos A, Friedländer M, Engström Y
RNA Biol · 2026 Dec · PMID 42089732 · Full text
Programmed stop codon readthrough (SCR) is a form of genetic re-coding, in which a near-cognate tRNA base-pairs with a stop codon, leading to the translation of a C-terminally extended protein. Recent studies revealed th...
Programmed stop codon readthrough (SCR) is a form of genetic re-coding, in which a near-cognate tRNA base-pairs with a stop codon, leading to the translation of a C-terminally extended protein. Recent studies revealed that SCR represents an evolutionarily conserved, spatio-temporally controlled mechanism of posttranscriptional gene regulation that requires -regulatory elements as well as -acting factors. In this study, we characterized -regulatory elements controlling programmed SCR of the POU3-family member (). Using S2 cell-based luciferase assays, we show that stop codon identity and the +4 to +9 nucleotide sequence are required but not sufficient for SCR regulation. Phylogenetic prediction identified an mRNA stem-loop in the 3' UTR, proximal to the readthrough UAG codon. Mutational analysis revealed that the distance from the stop codon as well as stem-loop stability, but not the underlying sequence identity, critically impact SCR. Similarly, the mRNA stem-loop promoted SCR in an model. We applied this information to refine computational prediction of SCR-associated mRNA stem-loops and show that these elements effectively promote SCR of heterologous mRNAs. These findings increase our understanding of SCR and the underlying regulatory mechanisms.
PrfH accelerates repair of colicin E3 - damaged translating ribosomes by RtcB2.
Maviza TP, Burmistrova NR, Grachev AA … +7 more , Khisambeeva E, Shiriaev DI, Zarechenskaia AS, Paleskava A, Konevega AL, Dontsova OA, Sergiev PV
RNA Biol · 2026 Dec · PMID 42080441 · Full text
Colicin E3 (E3-rRNAse) abolishes protein biosynthesis in bacteria by cleaving 16S rRNA in the decoding centre. The RtcB2-PrfH 16S rRNA repair module prevents cellular death upon exposure to E3-rRNAse in . Upon overexpres...
Colicin E3 (E3-rRNAse) abolishes protein biosynthesis in bacteria by cleaving 16S rRNA in the decoding centre. The RtcB2-PrfH 16S rRNA repair module prevents cellular death upon exposure to E3-rRNAse in . Upon overexpression, RtcB2 RNA ligase alone was capable of relieving growth, which was inhibited by E3-rRNAse. Using ribosome repair system based on recombinant components, we demonstrated that RtcB2 alone could repair E3-rRNAse cleaved 30S subunits and 70S ribosomes. The peptide chain release factor homolog (PrfH), which is able to hydrolyse peptidyl-tRNA bound by colicin-cleaved ribosomes, boosts RtcB2 ligation efficiency for damaged ribosomes engaged in translation.
Structure-driven function of plant lncRNAs: conserved RNA architectures in transcriptional and post-transcriptional regulation.
Shen Y, Dong Q, Ding Y … +1 more , Zhang H
RNA Biol · 2026 Dec · PMID 42041276 · Full text
Long noncoding RNAs (lncRNAs) have emerged as critical regulators of plant development, physiology, and environmental stress adaptation. Despite exhibiting limited primary sequence conservation across the plant kingdom,...
Long noncoding RNAs (lncRNAs) have emerged as critical regulators of plant development, physiology, and environmental stress adaptation. Despite exhibiting limited primary sequence conservation across the plant kingdom, emerging evidence underscores that plant lncRNA functionality is encoded at the level of RNA secondary structure, facilitating diverse modes of structure-mediated gene regulation. In this review, we synthesize recent advances in elucidating the structural conservation, and molecular functions of plant lncRNAs. We further discuss their expanding regulatory repertoire and assess their potential utility as innovative molecular tools for crop improvement.
Integrating bulk and single-cell transcriptomic data to construct a risk model for histidine metabolism-related epithelial cell features in lung adenocarcinoma, predicting prognosis and immune landscape.
Mao C, Zhou L
RNA Biol · 2026 Dec · PMID 42003422 · Full text
The rising incidence and mortality of lung adenocarcinoma (LUAD) present a significant public health challenge. Histidine, an essential amino acid, plays a pivotal role in metabolic processes, yet its specific contributi...
The rising incidence and mortality of lung adenocarcinoma (LUAD) present a significant public health challenge. Histidine, an essential amino acid, plays a pivotal role in metabolic processes, yet its specific contribution to LUAD pathogenesis remains to be elucidated. This study obtained bulk and single-cell RNA sequencing (scRNA-seq) data for LUAD from UCSC Xena and Code Ocean platforms, respectively. By integrating differential expression analysis, univariate/multivariate Cox analysis, and LASSO regression analysis, prognostic genes for LUAD were identified, and a prognostic risk model was constructed. Algorithms including ESTIMATE, ssGSEA, and CIBERSORT were employed to investigate immune heterogeneity across different groups. Furthermore, molecular subtypes of LUAD were identified through consensus clustering. This study, through the integration of bulk and scRNA-seq data, identified epithelial cells as the key effector cell population in LUAD, which can be further subdivided into four functionally heterogeneous subpopulations. Seven histidine metabolism-related epithelial cell-specific genes with prognostic significance in LUAD were identified (WIF1, GATA2, CD69, ID1, C4BPA, WFDC2, and CCL20), enabling the construction of a robust prognostic risk model. Immune infiltration analysis revealed that low-risk patients exhibited more robust immune infiltration and activity. Furthermore, cross-cancer exploratory evidence suggested potential sensitivity to CTLA-4 and PD-L1 inhibitors in this group. Furthermore, consensus clustering analysis successfully partitioned LUAD into two molecular subtypes exhibiting immune heterogeneity. The prognostic model constructed based on epithelial cell-specific genes associated with histidine metabolism effectively distinguishes LUAD patients and their immune characteristics, revealing epithelial cells as a key cell population regulating LUAD histidine metabolism.
RNA G-quadruplex-protein interactions: from nuclear RNA processing to cytoplasmic stress response and neurodegeneration.
Anastasakis DG, Hafner M
RNA Biol · 2026 Dec · PMID 41964251 · Full text
RNA G-quadruplexes (rG4s) are stable secondary structures formed by non-canonical Hoogsteen base-pairing of guanine-rich sequences in precursor and mature messenger and non-coding RNAs. We review evidence that rG4s exist...
RNA G-quadruplexes (rG4s) are stable secondary structures formed by non-canonical Hoogsteen base-pairing of guanine-rich sequences in precursor and mature messenger and non-coding RNAs. We review evidence that rG4s exist in two functionally distinct worlds. In the nucleus, rG4s fold co-transcriptionally to regulate gene expression and RNA processing and organizing membraneless organelles through liquid-liquid phase separation. Splicing regulation by rG4s is restricted to vertebrates and co-evolved with transcriptome complexity. In the cytoplasm, rG4s are actively maintained in an unfolded state by dedicated helicases and RNA-binding proteins, but fold upon stress to nucleate stress granules, that sequester mRNAs and sustain cell survival. When compartmentalization of rG4-protein interactions fails, cells lose both nuclear RNA processing control and cytoplasmic translational regulation and proper stress response. The same biophysical properties that make rG4s effective scaffolds for reversible phase separation in RNA processing, proteostasis, and acute stress become liabilities under chronic conditions: in ageing neurons, failure of rG4-protein homoeostasis transforms protective condensates into irreversible aggregates associated with α-synuclein, tau, TDP-43, and FUS pathology. We discuss the implications of a dynamic equilibrium of folded and unfolded rG4s in health and disease, with particular focus on their emerging roles in neurodegeneration.
Toward precision oncology: deciphering the circRNA-EMT axis in cancer and its therapeutic implications.
Lv Z, Xie G, Xu W
RNA Biol · 2026 Dec · PMID 41949207 · Full text
The epithelial-mesenchymal transition is a pivotal driver of cancer metastasis, the leading cause of mortality in solid tumours. Circular RNAs, a unique class of endogenous RNAs characterized by covalently closed loop st...
The epithelial-mesenchymal transition is a pivotal driver of cancer metastasis, the leading cause of mortality in solid tumours. Circular RNAs, a unique class of endogenous RNAs characterized by covalently closed loop structures and high stability, have emerged as key regulators in this process. Accumulating evidence reveals widespread dysregulation of circRNAs during EMT, where they function as critical modulators - either promoting or inhibiting the metastatic cascade. This review systematically elucidates the mechanisms by which circRNAs govern EMT, focusing on their interactions with classical signalling pathways (TGF-β, Wnt/β-catenin, and PI3K/AKT) and core EMT-transcription factors. Furthermore, we evaluate the dual promise of circRNAs as stable, disease-specific biomarkers for liquid biopsy and as novel therapeutic targets. Deciphering the complex circRNA-EMT regulatory network not only deepens our understanding of metastasis but also provides a rational framework for developing precision oncology strategies to intercept metastatic disease.
RNA export through the nuclear pore complex: pathways, mechanisms, and imaging strategies.
Fu D, Yu W, Zhang F … +3 more , Rush C, Tingey M, Yang W
RNA Biol · 2026 Dec · PMID 41943216 · Full text
Understanding how RNA molecules traverse the nuclear pore complex (NPC) is central to regulated gene expression because the NPC serves as the selective gateway for RNA export from the nucleus. Distinct RNA classes, inclu...
Understanding how RNA molecules traverse the nuclear pore complex (NPC) is central to regulated gene expression because the NPC serves as the selective gateway for RNA export from the nucleus. Distinct RNA classes, including tRNAs, snRNAs, miRNAs, lncRNAs, piRNAs, rRNAs, mRNAs, and circRNAs, follow biogenesis-coupled pathways and engage specific transport receptors and accessory factors to cross this barrier. Recent advances in single-molecule and super-resolution microscopy now enable direct, NPC-resolved visualization of transport for selected RNA species, allowing quantitative measurements of export kinetics, 3D trajectories through the pore, and interaction dynamics with NPC substructures. Here, we review and compare what has been learned from NPC-resolved imaging across RNA classes studied to date, highlighting both shared organizing principles and cargo-specific behaviours. We then describe an experimental and analytical toolbox for NPC-resolved studies of mRNA and pre-ribosomal particle export, including RNA-labelling strategies, major single-molecule and super-resolution modalities, and quantitative metrics used to extract transport parameters. Finally, we discuss key technical and conceptual barriers that currently limit extension to other RNA classes, particularly small and/or low-abundance RNAs, and outline practical strategies to overcome these constraints. Together, this review provides a unified framework for the next generation of single-molecule dissection of RNA dynamics at the nuclear pore.
NSUN2 as an emerging epigenetic regulator in cancer: from biomarker to therapeutic target.
Wei Y, Xu W, Bi Y … +6 more , Guo Q, Song P, Sun Y, Guo F, Gu P, Han Y
RNA Biol · 2026 Dec · PMID 41937349 · Publisher ↗
NOL1/NOP2/SUN domain family member 2 (NSUN2), a member of the RNA methyltransferase family responsible for catalysing 5-methylcytosine (m C) modifications, has been increasingly recognized as a key regulatory factor in t...
NOL1/NOP2/SUN domain family member 2 (NSUN2), a member of the RNA methyltransferase family responsible for catalysing 5-methylcytosine (m C) modifications, has been increasingly recognized as a key regulatory factor in the initiation and progression of cancer. A growing body of evidence indicates that NSUN2 is aberrantly expressed in multiple malignancies, such as hepatocellular carcinoma, breast cancer, and gastric cancer, where its overexpression is frequently associated with unfavourable clinical outcomes, increased tumour aggressiveness, and resistance to therapy. Through its mC modification activity, NSUN2 influences RNA stability, translational efficiency, and molecular interaction networks, thereby modulating critical oncogenic signalling pathways, including Wnt/β-catenin, PI3K/AKT, and epithelial-mesenchymal transition (EMT). Moreover, NSUN2 has been shown to interact with non-coding RNAs and epigenetic regulatory factors, contributing to the remodelling of the tumour microenvironment and facilitating immune evasion. Although NSUN2 is predominantly characterized by its tumour-promoting functions, emerging studies also suggest context-specific tumour-suppressive roles, highlighting its functional complexity in cancer biology. This review aims to summarize recent advances in understanding the molecular mechanisms underlying NSUN2 function, its clinical significance, and its potential as a biomarker or therapeutic target, while also discussing the challenges in translating these findings into clinical practice. A deeper understanding of NSUN2's diverse roles in carcinogenesis may provide novel insights into RNA epigenetics and inform the development of innovative strategies for cancer diagnosis and treatment.
Crosstalk between RNA secondary and three-dimensional structure prediction: a comprehensive study.
Wang D, Jiang Y, He L … +3 more , Zhang L, Zhou R, Zhang D
RNA Biol · 2026 Dec · PMID 41923428 · Full text
In recent years, various computational methods have been developed to predict the three-dimensional (3D) structures of RNAs. Due to its hierarchical folding property, RNA secondary (2D) structure is often used as input f...
In recent years, various computational methods have been developed to predict the three-dimensional (3D) structures of RNAs. Due to its hierarchical folding property, RNA secondary (2D) structure is often used as input for 3D structure prediction to improve accuracy and efficiency. However, the extent to which the accuracy of input 2D structure affects the performance of 3D structure prediction remains to be further investigated. Additionally, whether and how the input base-pairing interactions are modified during the 3D structure modelling process is another question worth exploring. To address these issues, here we comprehensively benchmark six representative 3D structure prediction models on extensive datasets, using 2D structures of varied accuracies as input. Our results indicate that there is a pervasive crosstalk between RNA 2D and 3D structure predictions, where the performance dependence of 3D structure prediction on the accuracy of input 2D structure is closely associated with the 3D model's ability to modify the input base-pairing interactions during structure modelling. Furthermore, we also observed that RNA 3D structure prediction performance is more sensitive to the occurrence of false positive base pairs in the input 2D structure than to true positive base pairs, suggesting a worthy direction to further improve the model performance.
CSDE1 promotes passenger strand cleavage of miR-486.
Arvand A, Ko Y, Patel MZ … +6 more , Hiscock L, Harvey LM, Simard MJ, Hope KJ, Shin C, Kakumani PK
RNA Biol · 2026 Dec · PMID 41905768 · Publisher ↗
Strand separation of the RNA duplex is vital for miRNA maturation, enabling the guide strand to form miRISC. The erythroid miRNA miR-486-5p requires AGO2-mediated catalytic cleavage of its passenger strand, miR-486-3p, b...
Strand separation of the RNA duplex is vital for miRNA maturation, enabling the guide strand to form miRISC. The erythroid miRNA miR-486-5p requires AGO2-mediated catalytic cleavage of its passenger strand, miR-486-3p, but the regulatory factors remain unclear. We identify CSDE1 as a cofactor that facilitates AGO2-dependent removal of the passenger strand and the maturation of miR-486-5p. Loss of CSDE1 increases miR-486-3p levels in leukaemia cells, decreases cleavage efficiency in vitro, and derepresses miR-486-5p targets. Reintroducing the full-length CSDE1 restores AGO2-dependent duplex cleavage in vitro, a function that depends on its N-terminal cold-shock domain (CSD1) for interaction with AGO2. Overall, these findings indicate that CSDE1 contributes to AGO2-mediated miR-486 strand separation, with implications for target gene silencing in leukaemia.
Hsa_circ_0000711 can serve as a novel biomarker for primary biliary cholangitis by promoting disease progression through the regulation of miR-185-5p and NFATc3.
Lu W, Li W, Wang P … +5 more , Cong P, Wang Z, Gao W, Sun G, Liu M
RNA Biol · 2026 Dec · PMID 41879109 · Full text
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune-mediated destruction of intrahepatic bile ducts. Emerging evidence suggests that circular RNAs (circRNAs) play regulato...
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune-mediated destruction of intrahepatic bile ducts. Emerging evidence suggests that circular RNAs (circRNAs) play regulatory roles in autoimmune diseases, but their involvement in PBC remains unclear. This study focused on the hsa_circ_0000711 and its potential mechanism in PBC pathogenesis. The study included 46 PBC patients, 40 healthy controls, and 40 patients with other liver diseases. Human intrahepatic biliary epithelial cells (HiBEpic) were treated with 1 mM glycochenodeoxycholic acid (GCDCA) to establish a PBC cell model. Hsa_circ_0000711 was overexpressed or knocked down using plasmid transfection and siRNA, respectively. Expression levels were analysed by qPCR/Western blot, cell viability by CCK-8, and hsa_circ_0000711-miR-185-5p interaction by luciferase assay. Serum hsa_circ_0000711 levels were significantly higher in PBC patients compared to healthy controls and other liver disease groups ( < 0.0001). GCDCA-treated HiBEpic cells showed increased expression of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) and nuclear factor of activated T cells 3 (NFATc3), along with decreased cell viability. Overexpression of hsa_circ_0000711 increased PDC-E2 and NFATc3 expression and worsened cellular injury, while its knockdown reversed these effects. The dual luciferase assay confirmed that hsa_circ_0000711 directly binds to miR-185-5p, suppressing its activity and thereby relieving the repression of NFATc3. Hsa_circ_0000711 promotes PBC progression by sponging miR-185-5p and upregulating NFATc3, leading to bile duct epithelial cell injury. These findings highlight its potential as a novel diagnostic biomarker and therapeutic target for PBC.
In silico unwinding of microRNA duplexes to evaluate thermodynamic end stabilities improves predictions of microRNA strand selection.
Medley JC, Zinovyeva A
RNA Biol · 2026 Dec · PMID 41873897 · Full text
microRNAs (miRNAs) are endogenous ~22 nucleotide long, non-coding RNAs that post-transcriptionally regulate gene expression. During miRNA biogenesis, stem-loop-containing miRNA precursors are enzymatically cleaved to for...
microRNAs (miRNAs) are endogenous ~22 nucleotide long, non-coding RNAs that post-transcriptionally regulate gene expression. During miRNA biogenesis, stem-loop-containing miRNA precursors are enzymatically cleaved to form a small RNA duplex. Cleavage positions are determined based on the position of structural motifs and junctions on the stem-loop precursor. The duplex end containing a favourable 5' nucleotide and lower thermodynamic stability is subsequently loading into an Argonaute protein. Typically, one duplex (guide) strand is retained in Argonaute and becomes functional whereas the other (passenger) strand is degraded. Therefore, accurate structural predictions of miRNA intermediates and quantification of duplex end stabilities are important towards understanding miRNA biogenesis. Here, we compiled predicted secondary structures for all miRNA hairpins and duplexes at physiologically relevant temperatures. We developed a new approach to calculate the thermodynamic stability of miRNA duplex ends, which resulted in improved predictions of miRNA strand selection. Our approach introduces hard constraints to folding algorithms to restrict base-pairing of terminal nucleotides, which improves modelling of duplex end unwinding. We propose that constrained RNA folding can be used to evaluate local stabilities within an RNA secondary structure.
AI foundation models for RNA biology.
Yu H, Ding Y
RNA Biol · 2026 Dec · PMID 41873866 · Full text
RNA biology is undergoing a transformative revolution driven by AI foundation models. These models learn the intricate relationships between RNA sequence, structure, and function by training on vast, diverse datasets spa...
RNA biology is undergoing a transformative revolution driven by AI foundation models. These models learn the intricate relationships between RNA sequence, structure, and function by training on vast, diverse datasets spanning millions of RNA molecules across various species. Through self-supervised learning on these sequences, these models acquire a generalizable understanding of RNA, which can then be fine-tuned for various downstream tasks, thereby enabling the decoding of functional rules embedded in RNA sequences. In this review, we provide a comprehensive guide to RNA foundation models. Using concrete examples of RNA biology, we begin with the concept of foundation models and review the importance of pre-training datasets, architectural innovations, self-supervised strategies, and fine-tuning approaches that allow general RNA representations to be translated into task-specific models. Crucially, we highlight how explainable AI (XAI) methods transform these models from black-box predictors into valuable discovery tools that reveal candidate cis-regulatory elements and structural motifs. As RNA foundation models keep advancing and integrating more multimodal biological data, they aim to uncover additional regulatory rules and functions encoded in RNA.
Reading the SINEs - functionality in noncoding RNA 'cheap genes'.
Zahavi EE, Fainzilber M
RNA Biol · 2026 Dec · PMID 41859929 · Full text
SINEs (Short Interspersed Nuclear Elements) are a class of retrotransposons, among the most prolific and transcriptionally active groups of repetitive elements. Rodent B1/B2-SINEs and primate Alu RNAs are upregulated in...
SINEs (Short Interspersed Nuclear Elements) are a class of retrotransposons, among the most prolific and transcriptionally active groups of repetitive elements. Rodent B1/B2-SINEs and primate Alu RNAs are upregulated in stress responses such as cellular heat shock or upon viral infection. Here, we review recent findings demonstrating that SINE RNAs have also integrated as adaptive regulators of gene expression in different biological contexts, particularly in nervous system lesion, degeneration and remodelling. These integral roles in physiological processes reinforce the concept that SINEs provide 'cheap genes' for evolutionary adaptation of non-coding RNA to biological function.
Change of guards: ELAVL proteins switch miRNA export responsibility to regulate differentiation of PC12 cells.
Ray S, Bhattacharyya SN, Mukherjee K
RNA Biol · 2026 Dec · PMID 41856545 · Full text
In the rat pheochromocytoma cell line PC12, which resembles sympathetic neurons, miRNA activity decreases during differentiation, and inactivation of the let-7a miRNP is essential for differentiation. We sought to examin...
In the rat pheochromocytoma cell line PC12, which resembles sympathetic neurons, miRNA activity decreases during differentiation, and inactivation of the let-7a miRNP is essential for differentiation. We sought to examine how let-7a activity is affected during differentiation. Extracellular vesicle-mediated miRNA export is a common strategy used by mammalian cells to regulate miRNA activity. HuR, an ELAVL protein that influences miRNA stability and activity by exporting Ago2-unbound miRNAs via extracellular vesicles, decreases in differentiating PC12 cells, whereas another ELAVL protein, HuD, increases. We found that HuD expression increases to takes up HuR's role in miRNA export regulation, thereby aiding differentiation by modulating specific miRNAs, such as let-7a and miR-125b. HuD binds these miRNAs, reducing their activity and promoting their export, thereby supporting PC12 differentiation. This switch in miRNA export responsibility from HuR to HuD may be both necessary and sufficient for neuronal differentiation.
Role of small intronic RNAs in the crosstalk between immune cells and β-cells during type 1 diabetes development.
Poddar S, Brozzi F, Cosentino C … +4 more , Jacovetti C, Guay C, Perrard J, Regazzi R
RNA Biol · 2026 Dec · PMID 41823267 · Full text
Small non-coding RNAs, such as microRNAs and tRNA-derived fragments, are key regulators of cellular processes, but the functions of small intronic RNAs (sinRNAs), a recently identified RNA class, remain largely unknown....
Small non-coding RNAs, such as microRNAs and tRNA-derived fragments, are key regulators of cellular processes, but the functions of small intronic RNAs (sinRNAs), a recently identified RNA class, remain largely unknown. Here, we report that two sinRNAs, sinR-D and sinR-T, are upregulated in pancreatic β-cells of NOD mice, a well-established model of type 1 diabetes. Using in vivo RNA-tagging, we demonstrate that these sinRNAs are packaged into extracellular vesicles released by infiltrating CD4 T lymphocytes and subsequently delivered to β-cells during the early stages of autoimmune attack. Functional analyses revealed that overexpression of sinR-T has little effect on β-cell viability, whereas sinR-D markedly increases β-cell apoptosis. This finding suggests that the transfer of sinR-D contributes to β-cell destruction and the onset of type 1 diabetes. Furthermore, pull-down experiments with biotinylated sinRNAs identified Ago2, a core component of the RNA-induced silencing complex (RISC), as a binding partner of sinR-D, indicating mechanistic parallels with microRNA-mediated regulation. Collectively, our data uncover a novel role for sinRNAs as extracellularly transferred regulators of β-cell fate, expanding the repertoire of small RNAs implicated in the initiation of type 1 diabetes.
Molecular insights into dynamic RNA quaternary assemblies.
Huang Z, Lin W, Wang L … +1 more , Su Z
RNA Biol · 2026 Dec · PMID 41819849 · Full text
Quaternary assembly of proteins frequently plays essential roles in biological processes. In contrast, natural RNA oligomers have rarely been reported. The majority of observed RNA quaternary structures are symmetric hom...
Quaternary assembly of proteins frequently plays essential roles in biological processes. In contrast, natural RNA oligomers have rarely been reported. The majority of observed RNA quaternary structures are symmetric homodimers, while recent studies have also revealed structures of heterodimers and symmetric homooligomers with more than two protomers. These higher-order assemblies adopt various intermolecular motifs including kissing-loops, pseudoknots, palindromic base-pairing, stacking, minor-groove interactions, and metal ion coordination that are found in RNA dimers. The dynamics in oligomerization vary across different segments of a single RNA as well as among different RNAs within the same family, which are primarily enabled by variable secondary structures, intermolecular motifs, and shape complementarity. These structural insights deepen our understanding of RNA multimerization mechanisms, paving the way for potential applications in condensate formation, RNA structure prediction, and therapeutic targeting and delivery.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe