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The Goldilocks state of transcriptional readthrough for chimeric splicing. 嵌合剪接的转录读通的金发姑娘状态。
IF 4.4
Transcription-Austin Pub Date : 2026-04-10 DOI: 10.1080/21541264.2026.2642485
Guillaume F Chanfreau
{"title":"The Goldilocks state of transcriptional readthrough for chimeric splicing.","authors":"Guillaume F Chanfreau","doi":"10.1080/21541264.2026.2642485","DOIUrl":"https://doi.org/10.1080/21541264.2026.2642485","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-13"},"PeriodicalIF":4.4,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
miRNA dynamics in development: orchestrators of gene expression and cell fate. 发育中的miRNA动力学:基因表达和细胞命运的协调者。
IF 4.4
Transcription-Austin Pub Date : 2026-02-01 Epub Date: 2026-03-18 DOI: 10.1080/21541264.2026.2643027
Vaishnav Vasudevan, Mathieu W Segonds, Martin J Simard
{"title":"miRNA dynamics in development: orchestrators of gene expression and cell fate.","authors":"Vaishnav Vasudevan, Mathieu W Segonds, Martin J Simard","doi":"10.1080/21541264.2026.2643027","DOIUrl":"10.1080/21541264.2026.2643027","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"67-86"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic and structural insights into TATA-Binding protein from cestodes. 绦虫中tata结合蛋白的基因组和结构分析。
IF 4.4
Transcription-Austin Pub Date : 2026-02-01 Epub Date: 2026-02-26 DOI: 10.1080/21541264.2026.2633940
Abraham Landa, Elisa Heredia-Gómez, Cristina González-Kulikova, Laura A Velázquez-Villegas, Oscar Rodríguez-Lima
{"title":"Genomic and structural insights into TATA-Binding protein from cestodes.","authors":"Abraham Landa, Elisa Heredia-Gómez, Cristina González-Kulikova, Laura A Velázquez-Villegas, Oscar Rodríguez-Lima","doi":"10.1080/21541264.2026.2633940","DOIUrl":"10.1080/21541264.2026.2633940","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"12-27"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ADAR-mediated tolerance and SOS splicing-mediated excision of transposable elements. adar介导的耐受性和SOS剪接介导的转座元件切除。
IF 4.4
Transcription-Austin Pub Date : 2026-02-01 Epub Date: 2026-02-26 DOI: 10.1080/21541264.2026.2638060
Qi Cao, Yuange Duan
{"title":"ADAR-mediated tolerance and SOS splicing-mediated excision of transposable elements.","authors":"Qi Cao, Yuange Duan","doi":"10.1080/21541264.2026.2638060","DOIUrl":"10.1080/21541264.2026.2638060","url":null,"abstract":"<p><p>Transposable elements (TEs) threaten genomic integrity, yet their pervasive presence indicates the limitations of existing silencing mechanisms. A recent paper in <i>Nature</i> (Zhao <i>et al</i>. 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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"28-31"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147291417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure-to-function relationships of RNA polymerases: recent advances in bacterial transcription termination. RNA聚合酶的结构-功能关系:细菌转录终止的最新进展。
IF 4.4
Transcription-Austin Pub Date : 2026-02-01 Epub Date: 2025-12-26 DOI: 10.1080/21541264.2025.2607221
Shuang Wang
{"title":"Structure-to-function relationships of RNA polymerases: recent advances in bacterial transcription termination.","authors":"Shuang Wang","doi":"10.1080/21541264.2025.2607221","DOIUrl":"10.1080/21541264.2025.2607221","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-11"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
XAB2: a link between RNA metabolism, DNA damage repair, and human health. XAB2: RNA代谢、DNA损伤修复和人类健康之间的联系。
IF 4.4
Transcription-Austin Pub Date : 2026-02-01 Epub Date: 2026-03-18 DOI: 10.1080/21541264.2026.2638065
Lucia Borszekova Pulzova, Miroslav Sabo, Miroslav Chovanec
{"title":"XAB2: a link between RNA metabolism, DNA damage repair, and human health.","authors":"Lucia Borszekova Pulzova, Miroslav Sabo, Miroslav Chovanec","doi":"10.1080/21541264.2026.2638065","DOIUrl":"10.1080/21541264.2026.2638065","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"32-66"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CGGBP1 from higher amniotes restricts cytosine methylation and drives a GC-bias in transcription factor-binding sites at repressed promoters. 来自高等羊膜的CGGBP1限制胞嘧啶甲基化,并在受抑制启动子的转录因子结合位点上驱动gc偏倚。
IF 4.4
Transcription-Austin Pub Date : 2025-08-01 Epub Date: 2025-07-31 DOI: 10.1080/21541264.2025.2533598
Praveen Kumar, Ishani Morbia, Aditi Lakshmi Satish, Subhamoy Datta, Umashankar Singh
{"title":"CGGBP1 from higher amniotes restricts cytosine methylation and drives a GC-bias in transcription factor-binding sites at repressed promoters.","authors":"Praveen Kumar, Ishani Morbia, Aditi Lakshmi Satish, Subhamoy Datta, Umashankar Singh","doi":"10.1080/21541264.2025.2533598","DOIUrl":"10.1080/21541264.2025.2533598","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"285-320"},"PeriodicalIF":4.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of the interaction of TATA-box binding protein 1 and 2 from Taenia solium to TATA-box: structural factors related to selectivity and affinity. 猪带绦虫TATA-box结合蛋白1和2与TATA-box的相互作用分析:与选择性和亲和力相关的结构因素。
IF 4.4
Transcription-Austin Pub Date : 2025-08-01 Epub Date: 2025-10-02 DOI: 10.1080/21541264.2025.2567199
Oscar Rodríguez-Lima, Juan Rodrigo Salazar, Laura A Velázquez-Villegas, María Fernanda Pérez-Téllez, Alonso Méndez-Pérez, Lucía Jiménez, Ricardo Miranda-Blancas, Elisa Heredia-Gómez, Marco A Loza-Mejía, Abraham Landa
{"title":"Analysis of the interaction of TATA-box binding protein 1 and 2 from <i>Taenia solium</i> to TATA-box: structural factors related to selectivity and affinity.","authors":"Oscar Rodríguez-Lima, Juan Rodrigo Salazar, Laura A Velázquez-Villegas, María Fernanda Pérez-Téllez, Alonso Méndez-Pérez, Lucía Jiménez, Ricardo Miranda-Blancas, Elisa Heredia-Gómez, Marco A Loza-Mejía, Abraham Landa","doi":"10.1080/21541264.2025.2567199","DOIUrl":"10.1080/21541264.2025.2567199","url":null,"abstract":"<p><p>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 <i>Taenia solium</i>, 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 <i>T. solium</i> 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 <i>T. solium</i>.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"321-336"},"PeriodicalIF":4.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perspective: divergent mRNA transcription machinery in Paramecium. 观点:草履虫中不同的mRNA转录机制。
IF 4.4
Transcription-Austin Pub Date : 2025-08-01 Epub Date: 2025-10-12 DOI: 10.1080/21541264.2025.2570066
Franziska Drews, Martin Simon
{"title":"Perspective: divergent mRNA transcription machinery in <i>Paramecium</i>.","authors":"Franziska Drews, Martin Simon","doi":"10.1080/21541264.2025.2570066","DOIUrl":"10.1080/21541264.2025.2570066","url":null,"abstract":"<p><p>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 <i>Paramecium</i> as an exciting model to study a divergent transcriptional machinery for vegetative mRNA and developmental ncRNA transcription.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"398-412"},"PeriodicalIF":4.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting HIV-1 transcription: road to a cure? 靶向HIV-1转录:通往治愈之路?
IF 4.4
Transcription-Austin Pub Date : 2025-08-01 Epub Date: 2025-11-14 DOI: 10.1080/21541264.2025.2586310
Liset de Vries, Robert-Jan Palstra, Tokameh Mahmoudi
{"title":"Targeting HIV-1 transcription: road to a cure?","authors":"Liset de Vries, Robert-Jan Palstra, Tokameh Mahmoudi","doi":"10.1080/21541264.2025.2586310","DOIUrl":"10.1080/21541264.2025.2586310","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"358-382"},"PeriodicalIF":4.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12716046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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