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200 papers
MicroRNA expression and functions in viral infections.
Skalsky RL
Transcription · 2026 Jul · PMID 42390919 · Publisher ↗
MicroRNAs (miRNAs) are small, noncoding RNAs that have emerged as powerful players in the post-transcriptional regulation of gene expression. In the context of viral infections, cellular miRNAs play significant roles in...
MicroRNAs (miRNAs) are small, noncoding RNAs that have emerged as powerful players in the post-transcriptional regulation of gene expression. In the context of viral infections, cellular miRNAs play significant roles in modulating the complex host responses to pathogens and have essential roles in shaping viral replication. Moreover, several virus families encode viral miRNAs that manipulate the host environment and can tap into miRNA-regulated gene networks. Viral antigen expression itself can be directly miRNA regulated, and infection outcomes are substantially shaped by the miRNA activities that influence host anti-viral defense mechanisms. This review discusses common themes for both human and viral miRNAs in viral infection processes, highlighting their dual functions in both suppressing and promoting viral life cycles.
Endogenous eukaryotic CHO-K1 cell promoters as tools to improve the production of a difficult-to-express recombinant protein.
Ardusso MB, Gugliotta A, Gastaldi V … +1 more , Prieto C
Transcription · 2026 Jun · PMID 42348756 · Publisher ↗
Recombinant proteins with applications in human and veterinary medicine are mainly produced in mammalian expression systems, particularly Chinese hamster ovary (CHO) cells. Although these cells enable proper folding and...
Recombinant proteins with applications in human and veterinary medicine are mainly produced in mammalian expression systems, particularly Chinese hamster ovary (CHO) cells. Although these cells enable proper folding and post-translational modifications, they often exhibit low specific productivity, which represents a critical limitation in large-scale biopharmaceutical manufacturing. Strong viral promoters, including CMV and its enhancer-enriched variant CMV+E, are commonly used to drive transgene expression. However, they are susceptible to epigenetic silencing and progressive loss of activity during prolonged culture, which can compromise yield stability. Endogenous host-cell promoters constitute a promising alternative, as they can maintain transgene expression in alignment with physiological and bioprocess regulatory mechanisms. Here, we assessed the activity of endogenous eukaryotic promoters previously identified in our laboratory from highly expressed CHO-K1 genes. The receptor-binding domain (RBD) of SARS-CoV-2 was selected as a model of a complex secretory glycoprotein domain. Our results demonstrate that the Hspa5 and Vim promoters enable sustained and high-level expression of recombinant RBD protein in CHO-K1 cells, achieving performance comparable to the enhancer-containing viral promoter CMV+E. Notably, Hspa5 and Vim are unoptimized genomic sequences lacking classical enhancers; nevertheless, their intrinsic stability and reduced susceptibility to silencing make them attractive regulatory elements for recombinant protein production. These findings highlight their potential for next-generation promoter engineering and for the development of long-term, high-yield mammalian expression systems for complex therapeutic proteins.
The Goldilocks state of transcriptional readthrough for chimeric splicing.
Chanfreau GF
Transcription · 2026 Apr · PMID 41962124 · Publisher ↗
Proper transcription termination coupled to pre-mRNA cleavage and polyadenylation is an important step in gene expression as it generates the 3'UTR of mRNAs and defines transcription units. Defective termination (transcr...
Proper transcription termination coupled to pre-mRNA cleavage and polyadenylation is an important step in gene expression as it generates the 3'UTR of mRNAs and defines transcription units. Defective termination (transcriptional readthrough) can suppress transcription of downstream genes by transcriptional interference but can also promote the production of chimeric transcripts, which contain the exons of upstream genes spliced to exons of downstream genes. This review will summarize current findings of chimeric splicing between exons of adjacent genes generated by transcriptional readthrough and the conditions that promote these events. Chimeric splicing can be facilitated by inactivation of factors that promote transcription termination or of specific splicing factors, particularly those involved in 3'-splice site recognition. This effect is due to the tight coupling between recognition of the terminal intron 3'-splice site and of the downstream polyadenylation sites, and its impact on transcriptional termination. Production of chimeric transcripts is also increased in cellular conditions that perturb transcription termination, such as cellular stress, treatment with the chemotherapeutic agent Imatinib or viral infections. However, not all conditions that promote transcriptional readthrough result in chimeric splicing, suggesting that the production of chimeric mRNAs requires a "Goldilocks" state of alteration of the transcriptional machinery that allows for transcriptional readthrough without a general reduction of splicing efficiency.
XAB2: a link between RNA metabolism, DNA damage repair, and human health.
Borszekova Pulzova L, Sabo M, Chovanec M
Transcription · 2026 Feb · PMID 41848795 · Full text
Cells have evolved multiple mechanisms to preserve genome integrity, collectively known as DNA damage response (DDR). Rather than acting separately, the DDR often interacts with transcription and mRNA splicing; however,...
Cells have evolved multiple mechanisms to preserve genome integrity, collectively known as DNA damage response (DDR). Rather than acting separately, the DDR often interacts with transcription and mRNA splicing; however, the underlying molecular mechanisms of this cross-talk are still poorly understood. Consistent with this, components of the splicing machinery are increasingly being recognized as factors with a direct role in sensing, signaling, and repairing DNA damage. Xeroderma pigmentosum group A-binding protein 2 (XAB2), which plays a well-characterized role in mRNA splicing, has also been implicated in the repair of transcription-blocking DNA lesions, transcription elongation, mRNA export, RNA surveillance, and R-loop processing. XAB2 is critical for a wide variety of biological processes, including the mitotic cell cycle, cell differentiation, stress responses, tissue homeostasis, and cellular senescence. However, the mechanism by which XAB2 functions outside of mRNA splicing remains unclear. In this review, we summarize the current knowledge of the biological processes affected by XAB2 in different cellular contexts. Furthermore, we discuss the link between XAB2 and human health, with a particular focus on cancer. This review aims to emphasize the importance of XAB2 and raise awareness of its physiological contributions.
miRNA dynamics in development: orchestrators of gene expression and cell fate.
Vasudevan V, Segonds MW, Simard MJ
Transcription · 2026 Feb · PMID 41847728 · Full text
MicroRNAs (miRNAs) are central regulators of gene expression, shaping cell fate, tissue identity, and organismal physiology. From the earliest stages of development through later processes of tissue differentiation, miRN...
MicroRNAs (miRNAs) are central regulators of gene expression, shaping cell fate, tissue identity, and organismal physiology. From the earliest stages of development through later processes of tissue differentiation, miRNAs operate within dynamic, context-dependent networks. Although the predominant role of miRNAs is to guide Argonaute-containing complexes to repress target mRNAs, the downstream consequences and mechanisms of action vary widely across developmental stages and tissue types. In this review, we examine the diverse roles of microRNAs in animal development across species and highlight emerging perspectives that are progressively refining our understanding of their function.
Genomic and structural insights into TATA-Binding protein from cestodes.
Landa A, Heredia-Gómez E, González-Kulikova C … +2 more , Velázquez-Villegas LA, Rodríguez-Lima O
Transcription · 2026 Feb · PMID 41755483 · Full text
The TATA-binding protein (TBP) is an essential component of the eukaryotic transcriptional machinery, yet little is known about the structure, evolution, and functional divergence of TBP paralogs in parasitic flatworms....
The TATA-binding protein (TBP) is an essential component of the eukaryotic transcriptional machinery, yet little is known about the structure, evolution, and functional divergence of TBP paralogs in parasitic flatworms. Here, we performed a comprehensive comparative analysis of TBP1 and TBP2 across cestode species of medical and veterinary relevance. Using genomic annotation, multiple sequence alignment, homology modeling, phylogenetics, electrostatic potential mapping, and protein - DNA docking complemented with molecular dynamics (MD) simulations, we reveal that both paralogs maintain a highly conserved genomic organization and the canonical TBP α/β saddle architecture. TBP1 exhibits moderate variability in sequence and electrostatic in peripheral regions, whereas TBP2 is more conserved, suggesting distinct evolutionary constraints. Despite paralog divergence, all cestode TBPs retain the key aromatic and basic residues required for minor-groove recognition of the TATA box and interaction with general transcription factors. Docking and MD simulations confirm a conserved pattern of TATA-binding across species, with TBP2 displaying exceptionally uniform interaction networks. Together, these findings provide genomic and structural data for TBPs in cestodes, suggesting the existence of paralog-specific regulatory roles and offering new insights into transcriptional control in parasitic flatworms.
ADAR-mediated tolerance and SOS splicing-mediated excision of transposable elements.
Cao Q, Duan Y
Transcription · 2026 Feb · PMID 41744490 · Full text
Transposable elements (TEs) threaten genomic integrity, yet their pervasive presence indicates the limitations of existing silencing mechanisms. A recent paper in (Zhao . 2025) discovered the SOS splicing system, which...
Transposable elements (TEs) threaten genomic integrity, yet their pervasive presence indicates the limitations of existing silencing mechanisms. A recent paper in (Zhao . 2025) discovered the SOS splicing system, which provides an RNA-level defense that excises DNA transposons from mRNAs, thereby restoring gene sequence. This spliceosome-independent pathway, mediated by AKAP17A, CAAP1, and RTCB, recognizes dsRNA hairpins formed by inverted terminal repeats (ITRs) and religates the resulting RNA fragments. From an evolutionary perspective, SOS splicing exemplifies a post-transcriptional error-correction mechanism that mitigates the deleterious consequence of TE insertions, paralleling the Constructive Neutral Evolution (CNE) framework. In contrast, ADAR-mediated A-to-I RNA editing suppresses the MDA5-triggered innate immune responses to TE-derived dsRNAs, effectively tolerating rather than eliminating TEs. There may be partial overlap between ADAR and SOS substrates. ADAR editing may delay but not prevent SOS splicing, while SOS excision removes ADAR substrates. The lethality of ADAR loss underscores its role as the mechanism mitigating purifying selection on TEs and thus may contribute to their genomic tolerance and proliferation. Collectively, while ADAR masks the harm of TEs, SOS splicing actively repairs the resulting damage, together illustrating a delicate evolutionary balance between TE tolerance and transcriptomic rescue.
Structure-to-function relationships of RNA polymerases: recent advances in bacterial transcription termination.
Wang S
Transcription · 2026 Feb · PMID 41451975 · Full text
Transcription termination is a highly regulated step which sets boundaries between genes and maintains genome integrity. Defects in transcription termination will cause unexpected expression of downstream genes and traff...
Transcription termination is a highly regulated step which sets boundaries between genes and maintains genome integrity. Defects in transcription termination will cause unexpected expression of downstream genes and traffic-jam of RNA polymerases with protein machineries. Termination occurs mainly in two types of mechanisms regarding whether it depends on molecular motor action, i.e. factor-dependent termination, or is induced solely by nucleic acid signals, i.e. intrinsic termination. In recent years, great efforts have been devoted to, and significant advances have been achieved in understanding the mechanisms of transcription termination. This review focuses on the topic of factor-dependent termination and intrinsic termination and highlights the recent progress in the structural and functional studies of RNA polymerases that are critical for transcription termination.
Rtr1 and RPAP2: versatile players in transcription and more.
Garrido-Godino AI, Navarro F
Transcription · 2025 · PMID 41313435 · Full text
Eukaryotic transcription of mRNAs and some non-coding RNAs is governed by RNA Polymerase II (RNA pol II). The full progression of RNA pol II across a gene - from promoter clearance through transcript elongation and termi...
Eukaryotic transcription of mRNAs and some non-coding RNAs is governed by RNA Polymerase II (RNA pol II). The full progression of RNA pol II across a gene - from promoter clearance through transcript elongation and termination - is dependent upon the post-translational modifications (PTMs) of its carboxy-terminal domain (CTD) and the dynamic recruitment of numerous trans-acting factors. Rtr1 in yeast and its human orthologue, RPAP2, have emerged as multifunctional regulators of RNA pol II. Despite evidence supporting their role as Ser5-specific CTD phosphatases, structural and biochemical studies have raised doubts about whether they are bona fide phosphatases or instead function as cofactors that influence the activity of established CTD phosphatases. Furthermore, both proteins have been implicated in processes ranging from RNA pol II biogenesis and nuclear transport to transcriptional elongation and termination. Notably, Rtr1's influence also extends to post-transcriptional events like mRNA stability. In this review, we describe the main functions attributed to Rtr1 and RPAP2, and discuss the role of the human homologue in various diseases.
Targeting HIV-1 transcription: road to a cure?
de Vries L, Palstra RJ, Mahmoudi T
Transcription · 2025 · PMID 41236888 · Full text
Human Immunodeficiency Virus 1 (HIV-1) is the causative agent for acquired immunodeficiency syndrome (AIDS). Antiretroviral therapy has turned HIV-1 from a lethal disease to a chronic condition but is not curative due to...
Human Immunodeficiency Virus 1 (HIV-1) is the causative agent for acquired immunodeficiency syndrome (AIDS). Antiretroviral therapy has turned HIV-1 from a lethal disease to a chronic condition but is not curative due to the persistence of a small reservoir of latently infected cells. The molecular mechanisms driving HIV-1 latency have been extensively studied, thus far largely focusing on transcriptional regulation. Here, we summarize well established and newly discovered mechanisms of HIV-1 latency, as well as how studies of the HIV-1 promoter have informed the broader transcription field. As a strategy toward HIV-1 cure, latency reversal agents (LRAs) have been developed to pharmacologically target blocks in HIV-1 transcription to achieve reactivation of viral gene expression. However, clinical studies indicate that LRAs have largely failed to sufficiently activate the reservoir such that viral protein is produced, and there was no reduction in the size of the viral reservoir. Indeed it has become clear that co- and post-transcriptional mechanisms are also at play to regulate HIV-1 gene expression and may also serve as attractive targetable blocks. We also outline recent developments in technologies allowing the ex vivo characterization of the HIV-1 reservoir in people living with HIV (PWH). These novel technologies enable us to interrogate the different molecular compartments such as integrated intact and defective proviral HIV-1 DNA, unspliced and spliced RNA, and protein levels that provide unprecedented new insight into latency mechanisms. Lastly, the potential of different transcription-targeting cure strategies is discussed in light of the contributions of co- and posttranscriptional blocks and the advent of Long Acting (LA)-ART.
Perspective: divergent mRNA transcription machinery in .
Drews F, Simon M
Transcription · 2025 · PMID 41077667 · Full text
Proper regulation of transcription involves not only quantitative control of RNA dosage but also ensuring the correct biochemical properties of transcripts. In all eukaryotes, the epigenetic landscape and the dynamic com...
Proper regulation of transcription involves not only quantitative control of RNA dosage but also ensuring the correct biochemical properties of transcripts. In all eukaryotes, the epigenetic landscape and the dynamic composition of the RNA Polymerase II complex (PolII) interact to control the transcription of translatable mRNA. Decades of research have described dogmatic rules for model organisms, such as the distribution of individual chromatin marks along the transcription unit or the hierarchical phosphorylation pattern in the C-terminal domain (CTD) of the largest PolII subunit RPB1. Besides this canonical mRNA transcription, there are exceptions; on the one hand, not all genes in a species follow the dogma, and on the other hand, there are species that show general divergence from the models, both in the epigenomic landscape and in the genetically encoded PolII. In the recent literature, protists in particular have shifted their attention as they show considerable differences in chromatin structure and PolII complex composition. Here, we aim to enlighten the transcription machinery of the unicellular ciliate as an exciting model to study a divergent transcriptional machinery for vegetative mRNA and developmental ncRNA transcription.
Analysis of the interaction of TATA-box binding protein 1 and 2 from to TATA-box: structural factors related to selectivity and affinity.
Rodríguez-Lima O, Salazar JR, Velázquez-Villegas LA … +7 more , Pérez-Téllez MF, Méndez-Pérez A, Jiménez L, Miranda-Blancas R, Heredia-Gómez E, Loza-Mejía MA, Landa A
Transcription · 2025 · PMID 41037282 · Full text
TATA-box binding protein (TBP) is a core subunit of the transcription factor TFIID and plays a pivotal role in recognizing the TATA-box in protein-coding genes, facilitating the assembly of the transcription preinitiatio...
TATA-box binding protein (TBP) is a core subunit of the transcription factor TFIID and plays a pivotal role in recognizing the TATA-box in protein-coding genes, facilitating the assembly of the transcription preinitiation complex. In , only one TBP isoform (TsTBP1) has been previously reported. Here, we identify and characterize a second isoform, TsTBP2, using a combination of molecular biology and bioinformatics approaches. TsTBP2 shares 42% primary sequence identity with TsTBP1 and exhibits distinct expression patterns between cysticerci and adult stages. To investigate the molecular determinants of DNA recognition, selectivity, and binding affinity, we performed molecular docking and molecular dynamics simulations for both TsTBPs with various TATA-box sequences. Our results reveal that TsTBP1 exhibits higher affinity for TATA-box sequences compared to the consensus AdML TATA-box (TATAAAAG), largely due to the specific interaction of critical phenylalanine residues with the DNA minor groove, which induces DNA bending and stabilizes the TBP-DNA complex. Furthermore, analysis of the Buckle parameter indicates that these Phe residues are the principal contributors to DNA distortion. To our knowledge, this study represents the first analysis of TBP selectivity and affinity in cestodes, providing insights into the molecular mechanisms underlying transcriptional regulation in .
Transcriptional regulation of gene modules in Epstein-Barr virus.
Lieberman PM
Transcription · 2025 · PMID 40983394 · Full text
Epstein-Barr Virus (EBV) establishes life-long latent infection in >90% of adults and is a causal agent for diverse cancers and autoimmune diseases. EBV has a complex life cycle in multiple different tissue types that in...
Epstein-Barr Virus (EBV) establishes life-long latent infection in >90% of adults and is a causal agent for diverse cancers and autoimmune diseases. EBV has a complex life cycle in multiple different tissue types that involve dynamic variations in viral gene expression. These gene expression changes account for the success of the virus in long-term persistence and evading host immune control, as well as its potential for driving cancer evolution and autoimmune disease. Here, we review some of the salient features of EBV gene regulation highlighting the many variations of viral transcription. We review recent advances in our understanding of the factors that bind and regulate EBV gene expression. Based on this diversity of viral transcription patterns, we propose that EBV genome consists of gene modules regulated by local promoter-proximal transcription factor combinations that are further regulated by distal regulatory interactions among the various modules that interact through architectural factors, such as CTCF and cohesion. These modules are likely to represent chromatin architectural domains, and can also interact with host chromosome domains that further regulate viral and host gene expression. We propose that this gene regulatory hierarchy provides EBV with necessary plasticity for viral persistence, as well as a strong potentiator for cancer and autoimmune disease.
CGGBP1 from higher amniotes restricts cytosine methylation and drives a GC-bias in transcription factor-binding sites at repressed promoters.
Kumar P, Morbia I, Satish AL … +2 more , Datta S, Singh U
Transcription · 2025 · PMID 40740140 · Full text
CGGBP1, a 20 kDa protein, has several functions associated with its DNA-binding through a C2H2 zinc finger. A range of studies have shown that GC richness, inter-strand G/C-skew and low cytosine methylation are associate...
CGGBP1, a 20 kDa protein, has several functions associated with its DNA-binding through a C2H2 zinc finger. A range of studies have shown that GC richness, inter-strand G/C-skew and low cytosine methylation are associated with CGGBP1 occupancy. The non-preference of any sequence motif as CGGBP1 binding site suggests widespread association of CGGBP1 with DNA including at potent transcription factor-binding sites (TFBSs) in promoter regions. The evolutionary advantage of such a design remains unclear. The regulatory interference by human CGGBP1 at TFBSs is supported by purifying selection in the DNA-binding domain of CGGBP1 and its requirement for gene repression as well as restriction of cytosine methylation at GC-rich TFBSs. Here, we describe an evolutionary trajectory of this property of CGGBP1 by combining global gene expression and cytosine methylation analyses on human cells expressing CGGBPs from four different vertebrates (representatives of coelacanth, reptiles, aves and mammals). We discover a potent cytosine methylation restriction by human CGGBP1 at some GC-rich TFBSs in repressed promoters. Further, we combine a high-throughput analysis of GC compositional bias of these CGGBP-regulated TFBSs from available orthologous sequences from a pool of over 100 species. We show that cytosine methylation restriction by CGGBP1 is tightly linked to GC retention in a set of TFBSs. Our experiments using four representative and three consensus forms of CGGBPs and orthology analyses of target gene promoters indicate that this property of CGGBPs has most likely evolved in higher amniotes (aves and mammals) with lineage-specific heterogeneities in lower amniotes (reptiles). ChIP-seq and C-T transition analysis in MeDIP-seq suggest that occupancy of CGGBP1 at these target TFBSs plays a crucial role in their low methylation, GC-biased evolution and associated functions in gene repression.
TFBSFootprinter: a multiomics tool for prediction of transcription factor binding sites in vertebrate species.
Barker HR, Parkkila S, Tolvanen ME
Transcription · 2025 · PMID 40646689 · Full text
BACKGROUND: Transcription factor (TF) proteins play a critical role in the regulation of eukaryotic gene expression via sequence-specific binding to genomic locations known as transcription factor binding sites (TFBSs)....
BACKGROUND: Transcription factor (TF) proteins play a critical role in the regulation of eukaryotic gene expression via sequence-specific binding to genomic locations known as transcription factor binding sites (TFBSs). Accurate prediction of TFBSs is essential for understanding gene regulation, disease mechanisms, and drug discovery. These studies are therefore relevant not only in humans but also in model organisms and domesticated and wild animals. However, current tools for the automatic analysis of TFBSs in gene promoter regions are limited in their usability across multiple species. To our knowledge, no tools currently exist that allow for automatic analysis of TFBSs in gene promoter regions for many species. METHODOLOGY AND FINDINGS: The TFBSFootprinter tool combines multiomic transcription-relevant data for more accurate prediction of functional TFBSs in 317 vertebrate species. In humans, this includes vertebrate sequence conservation (GERP), proximity to transcription start sites (FANTOM5), correlation of expression between target genes and TFs predicted to bind promoters (FANTOM5), overlap with ChIP-Seq TF metaclusters (GTRD), overlap with ATAC-Seq peaks (ENCODE), eQTLs (GTEx), and the observed/expected CpG ratio (Ensembl). In non-human vertebrates, this includes GERP, proximity to transcription start sites, and CpG ratio.TFBSFootprinter analyses are based on the Ensembl transcript ID for simplicity of use and require minimal setup steps. Benchmarking of the TFBSFootprinter on a manually curated and experimentally verified dataset of TFBSs produced superior results when using all multiomic data (average area under the receiver operating characteristic curve, 0.881), compared with DeepBind (0.798), DeepSEA (0.682), FIMO (0.817) and traditional PWM (0.854). The results were further improved by selecting the best overall combination of multiomic data (0.910). Additionally, we determined combinations of multiomic data that provide the best model of binding for each TF. TFBSFootprinter is available as Conda and Python packages.
Orphan nuclear receptor transcription factors as drug targets.
Safe S, Oany AR, Tsui WN … +8 more , Lee M, Srivastava V, Upadhyay S, Hailemariam A, Farkas E, Kakwan S, Kearns C, Sivaram G
Transcription · 2025 · PMID 40646688 · Full text
The nuclear receptor (NR) superfamily of ligand-activated receptors plays a key role in maintaining cellular homeostasis and in pathophysiology. NRs can be subdivided into functional activities structural similarity and...
The nuclear receptor (NR) superfamily of ligand-activated receptors plays a key role in maintaining cellular homeostasis and in pathophysiology. NRs can be subdivided into functional activities structural similarity and the existence of endogenous ligands. Most NRs are classified as those that are adopted orphan or orphan receptors which have only possible ligands or no identified endogenous ligands, respectively. In this review, the activities of the complete orphan receptor sub-family of transcription factors have been reviewed with a focus on the effects of possible endogenous (biochemicals), natural product-derived and synthetic ligands. Despite their lack of a bona-fide ligand, the orphan receptors bind structurally diverse compounds that exhibit tissue-specific agonist, antagonist and inverse agonist activities with potential for future development as clinical therapeutics for the treatment of multiple diseases.
Decoding complexity: tackling the challenge of how many transcription factors regulate a plant gene.
Gray J, Grotewold E
Transcription · 2025 · PMID 40566792 · Full text
The regulation of transcription is a major control point in the flow of information from the genome to the phenome. Central to this regulation are transcription factors (TFs), which bind specific DNA motifs in gene regul...
The regulation of transcription is a major control point in the flow of information from the genome to the phenome. Central to this regulation are transcription factors (TFs), which bind specific DNA motifs in gene regulatory regions. In both metazoans and plants, 5-7% of all genes encode TFs. Although individual TFs can recognize and regulate thousands of target genes, an important question remains: how many TFs are required to precisely control the expression of a single gene? In this review, we compare the regulation of gene expression in plants and metazoans, outline key methodologies for identifying genes recognized or regulated by TFs, and explore what is currently known about the number of TFs needed to define the expression of any given plant gene. As the volume of high-throughput sequencing data continues to grow exponentially, it becomes increasingly clear that transcriptional regulatory networks exhibit remarkable complexity, characterized by many targets influenced by each TF; and that many TFs, often several dozens, contribute to the regulation of individual genes.
GATA3 and E2F6 negatively regulate WDR77 expression to inhibit prostate cancer cell growth.
Brice R, Wang Z
Transcription · 2025 · PMID 40071854 · Full text
The WD repeat domain 77 (WDR77) protein plays a critical role in prostate development and dysregulation of WDR77 expression is associated with prostate tumorigenesis. This study investigated the regulatory effects of GAT...
The WD repeat domain 77 (WDR77) protein plays a critical role in prostate development and dysregulation of WDR77 expression is associated with prostate tumorigenesis. This study investigated the regulatory effects of GATA3 and E2F6 on WDR77 gene expression. A negative correlation between GATA3/E2F6 and WDR77 expression at both mRNA and protein levels was observed during prostate development and prostate tumorigenesis. Prostate cancer cells lost expression of GATA3 and E2F6 and re-expression of GATA3 and E2F6 resulted in a dose-dependent reduction in WDR77 expression and cell growth. Exogenous expression of WDR77 relieved the growth inhibition by GATA3. GATA3 and E2F6 directly interact with the promoter of the WDR77 gene in vitro and in vivo and repress WDR77 promoter activity. These results provide valuable insights into the molecular mechanisms governing WDR77 expression during prostate development and prostate tumorigenesis.
Rho-dependent termination: a bacterial evolutionary capacitor for stress resistance.
Worthan SB, Grant MI, Behringer MG
Transcription · 2025 · PMID 40044630 · Full text
Since the Modern Synthesis, interest has grown in resolving the "black box" between genotype and phenotype. Contained within this black box are highly plastic RNA and proteins with global effects on chromosome integrity...
Since the Modern Synthesis, interest has grown in resolving the "black box" between genotype and phenotype. Contained within this black box are highly plastic RNA and proteins with global effects on chromosome integrity and gene expression that serve as evolutionary capacitors - elements that enable the accumulation and buffering of genetic variation in normal conditions and reveal hidden genetic variation when induced by environmental stress. Discussion of evolutionary capacitors has primarily focused on eukaryotic translation factors and chaperones, such as Hsp90 and PSI+ prion. However, due to the coupling of transcription and translation in prokaryotes, transcription factors can be equally impactful in the modulation of gene expression and phenotypes. In this review, we discuss the prokaryotic transcription terminator Rho and how mutagenesis and plasticity of Rho influence epistasis, evolvability, and adaptation to stress in bacteria. We discuss the effects of variation in Rho generated by nature, laboratory mutagenesis, and experimental evolution; and how this variation is constrained or encouraged by Rho's extensive network of protein interactors. Exploring Rho's role as an evolutionary capacitor, along with identifying additional elements that can serve this function, can significantly advance our understanding of how organisms adapt to thrive in diverse environments.
The role of lncRNA in plant growth and domestication.
Gahlaut V, Jaiswal V
Transcription · 2025 · PMID 40035392 · Full text
The lncRNAs have deepened our understanding of crop domestication and improvement. These regulators influence key traits like yield, germination, and stress response. Future research should identify functional lncRNAs, e...
The lncRNAs have deepened our understanding of crop domestication and improvement. These regulators influence key traits like yield, germination, and stress response. Future research should identify functional lncRNAs, explore their interactions, and use CRISPR for targeted improvements. Understanding their roles in polyploid crops may enhance resilience and productivity.
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