IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080292.124

Sylvain Gervason, Sambuddha Sen, Jean-Luc Ravanat, Sylvain Caillat, Djemel Hamdane, Béatrice Golinelli-Pimpaneau

{"title":"Deciphering the influence of the [4Fe-4S] cluster of tRNA thiolation enzymes on tRNA binding.","authors":"Sylvain Gervason, Sambuddha Sen, Jean-Luc Ravanat, Sylvain Caillat, Djemel Hamdane, Béatrice Golinelli-Pimpaneau","doi":"10.1261/rna.080292.124","DOIUrl":"10.1261/rna.080292.124","url":null,"abstract":"Iron-sulfur clusters [Fe-S] play crucial roles in diverse biological reactions, often serving as prosthetic groups for enzymes. Specifically, certain tRNA-modifying enzymes utilize these clusters to catalyze the thiolation of specific nucleosides. While the participation of [4Fe-4S] clusters in such catalytic processes is known, their potential influence on tRNA binding remains unexplored. In this study, we examine the impact of the cluster on the affinity for tRNA of TtuI from the archeon Methanococcus maripaludis, an enzyme responsible for the formation of 4-thiouridine at position 8 in tRNAs of archaea and bacteria, as well as Escherichia coli TtcA that catalyzes the biosynthesis of 2-thiocytidine at position 32 in bacterial tRNAs. For this purpose, we compare the change of fluorescence properties of judiciously located tryptophans upon tRNA binding between the apo-enzyme (lacking the cluster) and the holo-enzyme (incorporating a reconstituted cluster). Our results indicate that the presence of the [4Fe-4S] cluster does not alter the affinity of the thiolases for tRNA, thus ruling out any direct involvement of the cluster in tRNA binding and emphasizing the purely catalytic role of the [4Fe-4S] cluster in tRNA thiolation.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"735-742"},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664467","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

RNA-binding protein Miso/CG44249 is crucial for minor splicing during oogenesis in Drosophila. rna结合蛋白Miso/CG44249对果蝇卵发生过程中的微小剪接至关重要。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080311.124

Yuki Taira, Li Zhu, Ryuya Fukunaga

{"title":"RNA-binding protein Miso/CG44249 is crucial for minor splicing during oogenesis in Drosophila.","authors":"Yuki Taira, Li Zhu, Ryuya Fukunaga","doi":"10.1261/rna.080311.124","DOIUrl":"10.1261/rna.080311.124","url":null,"abstract":"Pre-mRNA introns are removed by two distinct spliceosomes: the major (U2-type) spliceosome, which splices over 99.5% of introns, and the minor (U12-type) spliceosome, responsible for a rare class of introns known as minor introns. While the major spliceosome contains U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs) along with numerous associated proteins, the minor spliceosome comprises U11, U12, U4atac, U5, and U6atac snRNAs and includes specialized proteins. The function and regulation of the minor spliceosome are critical. Mutations in its specific component, RNA-binding protein RNPC3/65K, are linked to human diseases such as primary ovarian insufficiency. In this study, we identify RNA-binding protein Miso (CG44249), which shares 31% and 27% amino acid sequence identity with human RNPC3 and RBM41, respectively, as a key factor in minor splicing and oogenesis in Drosophila Miso associates with U11 and U12 snRNAs in ovaries. miso mutant females exhibit smaller ovaries, reduced germline stem cell numbers, disrupted oogenesis, reduced fecundity, and lower fertility. In miso mutant ovaries, significant minor intron retention is observed, accompanied by a reduction in spliced RNAs and protein products. Our findings establish Miso as a critical factor for minor intron splicing and underscore its essential role in Drosophila oogenesis.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"822-835"},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764952","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

Inconsistencies in the published rabbit ribosomal rRNAs: a proposal for uniformity in sequence and site numbering. 已发表的兔核糖体rRNAs的不一致性：序列和位点编号一致性的建议。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080294.124

Swastik De, Michelle Zhou, Zuben P Brown, Raymond N Burton-Smith, Yaser Hashem, Tatyana V Pestova, Christopher U T Hellen, Joachim Frank

引用次数: 0

Natural human tRNA^Ala anticodon variants mistranslate the genetic code. 天然人类tRNAAla反密码子变体错误翻译遗传密码。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080450.125

Rasangi Tennakoon, Teija M I Bily, Farah Hasan, Kyle S Hoffman, Patrick O'Donoghue

{"title":"Natural human tRNAAla anticodon variants mistranslate the genetic code.","authors":"Rasangi Tennakoon, Teija M I Bily, Farah Hasan, Kyle S Hoffman, Patrick O'Donoghue","doi":"10.1261/rna.080450.125","DOIUrl":"10.1261/rna.080450.125","url":null,"abstract":"Transfer RNAs (tRNAs) play an essential role in protein synthesis by linking the nucleic acid sequences of gene products to the amino acid sequences of proteins. There are >400 functional tRNA genes in humans, and adding to this diversity, there are many single-nucleotide polymorphisms in tRNAs across our population, including anticodon variants that mistranslate the genetic code. In human genomes, we identified three rare alanine tRNA (tRNAAla) variants with nonsynonymous anticodon mutations: tRNAAla CGC G35T, tRNAAla UGC G35A, and tRNAAla AGC C36T. Since alanyl-tRNA synthetase (AlaRS) does not recognize the anticodon, we hypothesized that these tRNAAla variants will misincorporate Ala at glutamate (Glu), valine (Val), and threonine (Thr) codons, respectively. We found that expressing the naturally occurring tRNAAla variants in human cells led to defects in protein production without a substantial impact on cell growth. Using mass spectrometry, we confirmed and estimated Ala misincorporation levels at Glu (0.7%), Val (5%), and Thr (0.1%) codons. Although Ala misincorporation was higher at Val codons, cells misincorporating Ala at Glu codons had the most severe defect in protein production. The data demonstrate the ability of natural human tRNAAla variants to generate mistranslation, leading to defects in protein production that depend on the nature of the amino acid replacement.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"791-806"},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674639","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 dual effect of FUBP1 on SPA lncRNA maturation. FUBP1对SPA lncRNA成熟的双重作用。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-16 DOI: 10.1261/rna.080341.124

Zheng-Hu Yang, Fang Nan, Guang Xu, Huang Wu, Meng-Yuan Wei, Li Yang, Ling-Ling Chen, Hao Wu

{"title":"A dual effect of FUBP1 on SPA lncRNA maturation.","authors":"Zheng-Hu Yang, Fang Nan, Guang Xu, Huang Wu, Meng-Yuan Wei, Li Yang, Ling-Ling Chen, Hao Wu","doi":"10.1261/rna.080341.124","DOIUrl":"10.1261/rna.080341.124","url":null,"abstract":"SPAs are noncanonical long noncoding RNAs (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated. Two SPAs are processed from a polycistronic transcript embedded in the human 15q11-q13 region related to Prader-Willi syndrome (PWS). Once produced, SPAs accumulate at their transcription site and sequester splicing factors to form PWS bodies that are involved in alternative splicing regulation. But how the processing of SPAs is regulated has remained obscure. Here, we identified that both far upstream element-binding protein 1 (FUBP1) and myelin expression factor 2 (MYEF2) were enriched in the PWS bodies; loss of either individually impaired SPAs' expression and dampened the size of PWS bodies in H9 and PA1 cells. Specifically, FUBP1, on the one hand, enhanced the transcription of SPA-embedded polycistronic transcripts by targeting the FUSE-like sequence upstream of the promoter, and on the other hand, was required for SPA1 splicing and maturation by binding the uridine (U)-rich intronic sequences. These findings suggest a comprehensive and distinct regulation of PWS region-derived SPA lncRNAs.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"807-821"},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731445","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

Corrigendum: An incredible life in science: Joseph G. Gall (1928-2024). 勘误：不可思议的科学生活：约瑟夫·g·加尔（1928-2024）。

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

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

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

EDC4 C-terminal domain scaffolds P-body assembly and links P-body dynamics to p53 mediated tumor suppression. EDC4 c端结构域支架p体组装并将p体动力学与p53介导的肿瘤抑制联系起来。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-13 DOI: 10.1261/rna.080561.125

Yu-Hsuan Cheng, Ting-Wen Chen, Wei-Chung Chiang, Jean-Cheng Kuo, Yi-Sheng Ho, Michelle Noble, Chung-Te Chang

{"title":"EDC4 C-terminal domain scaffolds P-body assembly and links P-body dynamics to p53 mediated tumor suppression.","authors":"Yu-Hsuan Cheng, Ting-Wen Chen, Wei-Chung Chiang, Jean-Cheng Kuo, Yi-Sheng Ho, Michelle Noble, Chung-Te Chang","doi":"10.1261/rna.080561.125","DOIUrl":"https://doi.org/10.1261/rna.080561.125","url":null,"abstract":"Processing bodies (P-bodies) are membrane-less organelles in eukaryotic cells that play a central role in mRNA metabolism, including mRNA decay, storage, and translational repression. However, the molecular mechanisms governing their assembly remain incompletely understood. Here, we identify the C-terminal domain of EDC4 as the minimal region required for P-body formation, with residues 1266-1401 driving phase separation and EDC4 condensation. To investigate the functional relevance of P-body integrity, we employed the microprotein Nobody (NBDY) as a selective perturbation tool. Our results revealed that the NBDY 22-41 peptide directly binds the EDC4 C-terminal domain and inhibits its self-association, thereby selectively dissolving P-bodies without affecting the canonical mRNA decay pathway. Using this tool, we further examined the impact of P-body disruption on gene expression. Transcriptome profiling combined with quantitative validation revealed that P-body loss activates the p53 pathway and enhances the stability of associated transcripts. Consistent with these findings, clinical data show that NBDY overexpression is associated with p53 pathway activation in various cancers, and the NBDY 22-41 fragment reduces tumor cell proliferation and invasion, suggesting a potentially complex role of P-body dynamics in cancer biology. Together, our study defines the EDC4 C-terminal domain as a core scaffold for P-body assembly and uncovers a regulatory role of P-body dynamics in p53-mediated gene expression, with potential implications for cancer biology.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alu RNA pseudoknot alterations influence SRP9/SRP14 association. Alu RNA假结改变影响SRP9/SRP14的关联。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-09 DOI: 10.1261/rna.080359.124

Daniel Gussakovsky, Mira J F Brown, Higor Sette Pereira, Markus Meier, Gay Pauline Padilla-Meier, Nicole A Black, Evan P Booy, Jörg Stetefeld, Trushar R Patel, Sean A McKenna

{"title":"Alu RNA pseudoknot alterations influence SRP9/SRP14 association.","authors":"Daniel Gussakovsky, Mira J F Brown, Higor Sette Pereira, Markus Meier, Gay Pauline Padilla-Meier, Nicole A Black, Evan P Booy, Jörg Stetefeld, Trushar R Patel, Sean A McKenna","doi":"10.1261/rna.080359.124","DOIUrl":"https://doi.org/10.1261/rna.080359.124","url":null,"abstract":"There are over 1 million Alu elements in the human genome which can be transcribed into discrete, RNA polymerase III transcribed non-coding Alu RNAs. These Alu RNAs often interact with and are regulated by the protein heterodimer SRP9/SRP14. This interaction is dependent on a 5' pseudoknot domain in the Alu RNA that is thought to be held together by a canonical nucleotide triad within a U-turn motif. Herein, we discover a significant reduction in BC200 expression after mutation of a critical guanosine in the U-turn motif within its pseudoknot domain. We studied a recently discovered short human Alu RNA, EB120 that lacked the canonical Alu RNA U-turn nucleotide triad. We tested the expression of EB120 in 18 different human cell lines and tissues. EB120 was found to lack association with SRP9/SRP14 in a cellular context. Small angle X-ray scattering followed by atomistic computation structure prediction suggests the BC200 Alu domain and its U-turn mutant both possess a canonical Alu RNA fold, while EB120 lacks one. Our results highlight the structural diversity of Alu RNA, and the impact mutations may have on Alu RNA function.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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