IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080473.125

Svetlana Deryusheva, Ji-Long Liu, Zehra F Nizami, Gaëlle J S Talross, Susan A Gerbi

引用次数: 0

Repression of AGO1 by AGO2 via let-7 microRNAs facilitates embryonic stem cell differentiation. AGO2通过let-7 microrna抑制AGO2促进胚胎干细胞分化。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080426.125

Gabrielle M Schuh, Katharine R Maschhoff, Annastasia Minor, Wenqian Hu

{"title":"Repression of AGO1 by AGO2 via let-7 microRNAs facilitates embryonic stem cell differentiation.","authors":"Gabrielle M Schuh, Katharine R Maschhoff, Annastasia Minor, Wenqian Hu","doi":"10.1261/rna.080426.125","DOIUrl":"10.1261/rna.080426.125","url":null,"abstract":"Argonaute (AGO) proteins are critical regulators of gene expression. Of the four AGOs in mammals, AGO1 and AGO2 are expressed in mouse embryonic stem cells (mESCs). These two proteins have opposing functions in controlling mESCs' fate decisions between pluripotency and differentiation. AGO2 promotes differentiation predominantly via the let-7 microRNAs, whereas AGO1 maintains pluripotency via modulating protein folding independent of small RNAs. These recent findings raise the question of whether and how these two AGOs are mutually regulated in mESCs. Here, using loss-of-function and gain-of-function approaches, we show that AGO2 represses the expression of AGO1 mRNA via a conserved let-7-microRNA-binding site in its 3' UTR. Mutating this binding site at the endogenous locus abolishes the AGO2-mediated repression of AGO1 mRNA and compromises the exit pluripotency of mESCs. These results indicate that the posttranscriptional regulation of AGO1 by AGO2 and let-7 microRNAs is important for stem cell differentiation, but also reveal a regulatory mechanism between the two AGO paralogs with opposing functions in controlling stem cell fate decisions.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"772-780"},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Terminal nucleotidyltransferase Tent2 microRNA A-tailing enzyme regulates excitatory/inhibitory balance in the hippocampus. 末端核苷酸转移酶Tent2 microRNA A尾酶调节海马的兴奋/抑制平衡

IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080240.124

Patrycja Wardaszka-Pianka, Bozena Kuzniewska, Natalia GumiNska, Anna Hojka-Osinska, Monika Puchalska, Jacek Milek, Aleksandra Stawikowska, Pawel Krawczyk, Francois P Pauzin, Tomasz Wojtowicz, Kasia Radwanska, Clive R Bramham, Andrzej Dziembowski, Magdalena Dziembowska

{"title":"Terminal nucleotidyltransferase Tent2 microRNA A-tailing enzyme regulates excitatory/inhibitory balance in the hippocampus.","authors":"Patrycja Wardaszka-Pianka, Bozena Kuzniewska, Natalia GumiNska, Anna Hojka-Osinska, Monika Puchalska, Jacek Milek, Aleksandra Stawikowska, Pawel Krawczyk, Francois P Pauzin, Tomasz Wojtowicz, Kasia Radwanska, Clive R Bramham, Andrzej Dziembowski, Magdalena Dziembowska","doi":"10.1261/rna.080240.124","DOIUrl":"10.1261/rna.080240.124","url":null,"abstract":"One of the posttranscriptional mechanisms regulating the stability of RNA molecules involves the addition of nontemplated nucleotides to their 3' ends, a process known as RNA tailing. To systematically investigate the physiological consequences of terminal nucleotidyltransferase TENT2 absence on RNA 3' end modifications in the mouse hippocampus, we developed a new Tent2 knockout mouse. Electrophysiological measurements revealed increased excitability in Tent2 KO hippocampal neurons, and behavioral analyses showed decreased anxiety and improved fear extinction in these mice. At the molecular level, we observed changes in miRNAs' monoadenylation in Tent2 KO mouse hippocampus, but found no effect of the TENT2 loss on the mRNAs' total poly(A) tail length, as measured by direct nanopore RNA sequencing. Moreover, differential expression analysis revealed transcripts related to synaptic transmission to be downregulated in the hippocampus of Tent2 knockout mice. These changes may explain the observed behavioral and electrophysiological alterations. Our data thus establish a link between TENT2-dependent miRNA tailing and the balance of inhibitory and excitatory neurotransmission.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"756-771"},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A general RNA-templated RNA extension activity of E. coli RNA polymerase. 大肠杆菌RNA聚合酶的一般RNA模板RNA延伸活性。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080238.124

Drew Galls, Andreas U Mueller, Emily Greenwald, Andrew Z Fire

{"title":"A general RNA-templated RNA extension activity of E. coli RNA polymerase.","authors":"Drew Galls, Andreas U Mueller, Emily Greenwald, Andrew Z Fire","doi":"10.1261/rna.080238.124","DOIUrl":"10.1261/rna.080238.124","url":null,"abstract":"Multisubunit \"DNA-dependent\" RNA polymerases (RNAPs) have noncanonical RNA-directed RNA synthesis activity; this allows the synthesis of complementary RNA from RNA templates. Such noncanonical RNAP activities are biologically significant, serving RNA pathogens such as hepatitis delta virus (HDV) and contributing to cellular gene regulation. Despite the broad biological implications of these processes, our understanding of the underlying RNAP mechanisms remains incomplete. Using Escherichia coli RNAP, a multisubunit RNAP, as a model, we describe here the general RNA-templated RNA extension activity of that enzyme. Our data argue that the 3' end of an added RNA template can fold back and pair with upstream bases in the template, creating an intramolecular primer:template duplex as short as 1-2 base pairs. The RNAP then extends this intramolecular duplex, incorporating nucleotides complementary to the template. RNA-templated RNA extension occurred in minutes and did not appear to be suppressed by the presence of a promoter-containing DNA template. Excepting oligonucleotides implicitly designed to prevent any possibility of 3' end self-priming, every RNA template we tested could be extended by the enzyme, highlighting the general nature of this reaction. These data define a general activity of a cellular RNAP. Unrestricted, this activity could contribute to the emergence and replication of RNA-based agents such as HDV and viroids; if highly regulated, the activity could limit these same elements.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"663-678"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conformational heterogeneity in the dGsw purine riboswitch: role of Mg²⁺ and 2'-dG in aptamer folding. dGsw 嘌呤核糖开关的构象异质性：Mg²⁺和 2'-dG 在适配体折叠中的作用。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080274.124

Susmit Narayan Chaudhury, Erdong Ding, Nathan E Jespersen, José N Onuchic, Karissa Y Sanbonmatsu

{"title":"Conformational heterogeneity in the dGsw purine riboswitch: role of Mg2+ and 2'-dG in aptamer folding.","authors":"Susmit Narayan Chaudhury, Erdong Ding, Nathan E Jespersen, José N Onuchic, Karissa Y Sanbonmatsu","doi":"10.1261/rna.080274.124","DOIUrl":"10.1261/rna.080274.124","url":null,"abstract":"Recent advancements in RNA structural biology have focused on unraveling the complexities of noncoding mRNA like riboswitches. These cis-acting regulatory regions undergo structural changes in response to specific cellular metabolites, leading to up- or downregulation of downstream genes. The purine riboswitch family regulates prokaryotic genes involved in purine degradation and biosynthesis. They feature an aptamer domain organized around a three-way helical junction, where ligand encapsulation occurs at the junctional core. We chemically probed the aptamer domain of the 2'-dG-sensing purine riboswitch from Mesoplasma florum (dGsw) under various solution conditions to understand how Mg2+ and 2'-dG influence riboswitch folding. We find that 2'-dG binding strongly depends on Mg2+, indicating that Mg2+ is essential for priming dGsw for ligand interactions. We identified a previously undescribed sequence in the 5' tail of dGsw that is complementary to a conserved helix. The inclusion of this region led to intramolecular competition between the alternate helix, Palt, and P1. Mutational analysis confirmed that the 5' flanking end of the aptamer domain forms an alternate helix in the absence of ligand. Molecular dynamics simulations revealed that this alternative conformation is stable. This helix may facilitate the formation of an antiterminator helix by opening the three-way junction surrounding the 2'-dG binding site. Our study establishes the importance of a closed terminal P1 helix conformation for metabolite binding and suggests that the delicate interplay between P1 and Palt fine-tunes downstream gene regulation. These insights offer a new perspective on riboswitch structure and enhance our understanding of the role that a conformational ensemble plays in riboswitch activity and regulation.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"724-733"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circuit logic: interdependent RNA modifications shape mRNA and noncoding RNA structure and function. 电路逻辑：相互依赖的RNA修饰形成mRNA和非编码RNA的结构和功能。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080421.125

Jennifer Porat

{"title":"Circuit logic: interdependent RNA modifications shape mRNA and noncoding RNA structure and function.","authors":"Jennifer Porat","doi":"10.1261/rna.080421.125","DOIUrl":"10.1261/rna.080421.125","url":null,"abstract":"Continued advances in high-throughput detection of posttranscriptional RNA modifications have enabled large-scale, mechanistic studies into the importance of RNA modifications in regulating the structure, function, and stability of coding and noncoding RNAs. More recently, this has expanded beyond investigations of independent single modifications, revealing the breadth of modification complexities in single transcripts and the biogenesis pathways involved that lead to coordinately modified RNA species. This has resulted in the concept of modification circuits, where one modification can promote or inhibit the subsequent installation of other modifications, or when modifications are coordinated across different RNA species. These circuits play important roles in the biogenesis of multistepped posttranscriptional modifications, modulate ribonucleoprotein complex formation and conformational switches, and mediate codon-biased translation through the coordination of mRNA and tRNA modifications. Here, I review evidence of complex modification circuits in mRNA and noncoding RNA and highlight open questions concerning the molecular mechanisms giving rise to modification circuits and their importance in the context of RNA processing and maturation.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"613-622"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice. 细胞质外泌体催化亚基DIS3L是小鼠发育所必需的，但不是细胞活力。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080350.124

Michał Brouze, Marcin Szpila, Areta Czerwińska, Wiktor Antczak, Seweryn Mroczek, Tomasz M Kuliński, Anna Hojka-Osińska, Dominik Cysewski, Olga Gewartowska, Dorota Adamska, Jakub Gruchota, Ewa Borsuk, Andrzej Dziembowski

{"title":"DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice.","authors":"Michał Brouze, Marcin Szpila, Areta Czerwińska, Wiktor Antczak, Seweryn Mroczek, Tomasz M Kuliński, Anna Hojka-Osińska, Dominik Cysewski, Olga Gewartowska, Dorota Adamska, Jakub Gruchota, Ewa Borsuk, Andrzej Dziembowski","doi":"10.1261/rna.080350.124","DOIUrl":"10.1261/rna.080350.124","url":null,"abstract":"Among numerous enzymes involved in RNA decay, processive exoribonucleases are the most prominent group responsible for the degradation of entire RNA molecules. The role of mammalian cytoplasmic 3'-5' exonuclease DIS3L at the organismal level remained unknown. Herein, we established knock-in and knockout (KO) mouse models to study DIS3L functions in mice. DIS3L in mice is indeed a subunit of the cytoplasmic exosome complex, the disruption of which leads to severe embryo degeneration and death in mice soon after implantation. These changes could not be prevented by supplementing extraembryonic tissue with functional DIS3L through the construction of chimeric embryos. Preimplantation Dis3l -/- embryos were unaffected in their morphology and ability to produce functional embryonic stem (ES) cells, showing that DIS3L is not essential for cell viability. There were also no major changes at the transcriptome level for both ES cells and blastocysts, as revealed by RNA-seq experiments. Notably, however, Dis3l KO led to inhibition of global protein synthesis. These results point to the essential role of DIS3L in mRNA metabolism, which is crucial for proper protein synthesis during embryo development.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"646-662"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Different RNA recognition by ProQ and FinO depends on the sequence surrounding intrinsic terminator hairpins. ProQ和FinO识别RNA的不同取决于内在终止子发夹周围的序列。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080206.124

Maria D Mamońska, Maciej M Basczok, Ewa M Stein, Julia Kurzawska, Mikołaj Olejniczak

引用次数: 0

Prevention of ribozyme catalysis through cDNA synthesis enables accurate RT-qPCR measurements of context-dependent ribozyme activity. 通过cDNA合成防止核酶催化使RT-qPCR准确测量上下文依赖的核酶活性。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080243.124

Nina Y Alperovich, Olga B Vasilyeva, Samuel W Schaffter

{"title":"Prevention of ribozyme catalysis through cDNA synthesis enables accurate RT-qPCR measurements of context-dependent ribozyme activity.","authors":"Nina Y Alperovich, Olga B Vasilyeva, Samuel W Schaffter","doi":"10.1261/rna.080243.124","DOIUrl":"10.1261/rna.080243.124","url":null,"abstract":"Self-cleaving ribozymes are important tools in synthetic biology, biomanufacturing, and nucleic acid therapeutics. These broad applications deploy ribozymes in many genetic and environmental contexts, which can influence activity. Thus, accurate measurements of ribozyme activity across diverse contexts are crucial for validating new ribozyme sequences and ribozyme-based biotechnologies. Ribozyme activity measurements that rely on RNA extraction, such as RNA sequencing or reverse transcription-quantitative polymerase chain reaction (RT-qPCR), are generalizable to most applications and have high sensitivity. However, the activity measurement is indirect, taking place after RNA is isolated from the environment of interest and copied to DNA. Thus, these measurements may not accurately reflect the activity in the original context. Here, we develop and validate an RT-qPCR method for measuring context-dependent ribozyme activity using a set of self-cleaving RNAs for which context-dependent ribozyme cleavage is known in vitro. We find that RNA extraction and reverse transcription conditions can induce substantial ribozyme cleavage, resulting in incorrect activity measurements with RT-qPCR. To restore the accuracy of the RT-qPCR measurements, we introduce an oligonucleotide into the sample preparation workflow that inhibits ribozyme activity. We then apply our method to measure ribozyme cleavage of RNAs produced in Escherichia coli These results have broad implications for many ribozyme measurements and technologies.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"633-645"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Positioning of sperm tail longitudinal columns depends on NSUN7, an RNA-binding protein destabilizing elongated spermatid transcripts. 精子尾部纵向柱的定位依赖于Nsun7，一种破坏长形精子转录本稳定的RNA结合蛋白。

IF 4.2 3区生物学

RNA Pub Date : 2025-04-16 DOI: 10.1261/rna.080320.124

Ekaterina A Guseva, Olga A Averina, Sergey V Isaev, Philipp I Pletnev, Elizaveta E Bragina, Oleg A Permyakov, Vitaly S Buev, Anastasia V Priymak, Mariia A Emelianova, Lizaveta Pshanichnaya, Evgeny A Romanov, Svetlana E Novikova, Kirill S Petriukov, Anna Ya Golovina, Olga O Grigorieva, Vasily N Manskikh, Diana S Korshunova, Yuliya Yu Silaeva, Alexey V Deykin, Maria P Rubtsova, Victor G Zgoda, Alexander M Mazur, Egor B Prokhortchouk, Olga A Dontsova, Petr V Sergiev

{"title":"Positioning of sperm tail longitudinal columns depends on NSUN7, an RNA-binding protein destabilizing elongated spermatid transcripts.","authors":"Ekaterina A Guseva, Olga A Averina, Sergey V Isaev, Philipp I Pletnev, Elizaveta E Bragina, Oleg A Permyakov, Vitaly S Buev, Anastasia V Priymak, Mariia A Emelianova, Lizaveta Pshanichnaya, Evgeny A Romanov, Svetlana E Novikova, Kirill S Petriukov, Anna Ya Golovina, Olga O Grigorieva, Vasily N Manskikh, Diana S Korshunova, Yuliya Yu Silaeva, Alexey V Deykin, Maria P Rubtsova, Victor G Zgoda, Alexander M Mazur, Egor B Prokhortchouk, Olga A Dontsova, Petr V Sergiev","doi":"10.1261/rna.080320.124","DOIUrl":"10.1261/rna.080320.124","url":null,"abstract":"Spermatozoid's flagella assemble in transcriptionally silent spermatids and thus depend on posttranscriptional regulation of gene expression. Mutations in Nsun7 gene are known to cause male infertility in human and mice. We identified m5C-specific NSUN7 RNA methyltransferase as a protein present in elongated spermatids and interacting with RNAs specific for this type of spermatozoid's precursor cells. Inactivation of the Nsun7 gene in mice leads to upregulation of its RNA interactors, thus indicating that NSUN7 downregulates a set of RNAs in the elongated spermatids. A physiologic consequence of Nsun7 gene knockout is male infertility, which is mechanistically explained by the observed mispositioning of longitudinal columns relative to the axonemal microtubular doublets leading to a motility defect.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"709-723"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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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