Pub Date : 2023-08-07DOI: 10.3389/frnar.2023.1244554
Maxime Wery, Ugo Szachnowski, Sara Andjus, Alvaro de Andres-Pablo, Antonin Morillon
The expression of yeast long non-coding (lnc)RNAs is restricted by RNA surveillance machineries, including the cytoplasmic 5'-3' exonuclease Xrn1 which targets a conserved family of lncRNAs defined as XUTs, and that are mainly antisense to protein-coding genes. However, the co-factors involved in the degradation of these transcripts and the underlying molecular mechanisms remain largely unknown. Here, we show that two RNA helicases, Dbp2 and Mtr4, act as global regulators of XUTs expression. Using RNA-Seq, we found that most of them accumulate upon Dbp2 inactivation or Mtr4 depletion. Mutants of the cytoplasmic RNA helicases Ecm32, Ski2, Slh1, Dbp1, and Dhh1 did not recapitulate this global stabilization of XUTs, suggesting that XUTs decay is specifically controlled by Dbp2 and Mtr4. Notably, Dbp2 and Mtr4 affect XUTs independently of their configuration relative to their paired-sense mRNAs. Finally, we show that the effect of Dbp2 on XUTs depends on a cytoplasmic localization. Overall, our data indicate that Dbp2 and Mtr4 are global regulators of lncRNAs expression and contribute to shape the non-coding transcriptome together with RNA decay machineries.
{"title":"The RNA helicases Dbp2 and Mtr4 regulate the expression of Xrn1-sensitive long non-coding RNAs in yeast.","authors":"Maxime Wery, Ugo Szachnowski, Sara Andjus, Alvaro de Andres-Pablo, Antonin Morillon","doi":"10.3389/frnar.2023.1244554","DOIUrl":"https://doi.org/10.3389/frnar.2023.1244554","url":null,"abstract":"<p><p>The expression of yeast long non-coding (lnc)RNAs is restricted by RNA surveillance machineries, including the cytoplasmic 5'-3' exonuclease Xrn1 which targets a conserved family of lncRNAs defined as XUTs, and that are mainly antisense to protein-coding genes. However, the co-factors involved in the degradation of these transcripts and the underlying molecular mechanisms remain largely unknown. Here, we show that two RNA helicases, Dbp2 and Mtr4, act as global regulators of XUTs expression. Using RNA-Seq, we found that most of them accumulate upon Dbp2 inactivation or Mtr4 depletion. Mutants of the cytoplasmic RNA helicases Ecm32, Ski2, Slh1, Dbp1, and Dhh1 did not recapitulate this global stabilization of XUTs, suggesting that XUTs decay is specifically controlled by Dbp2 and Mtr4. Notably, Dbp2 and Mtr4 affect XUTs independently of their configuration relative to their paired-sense mRNAs. Finally, we show that the effect of Dbp2 on XUTs depends on a cytoplasmic localization. Overall, our data indicate that Dbp2 and Mtr4 are global regulators of lncRNAs expression and contribute to shape the non-coding transcriptome together with RNA decay machineries.</p>","PeriodicalId":73105,"journal":{"name":"Frontiers in RNA research","volume":"1 ","pages":"1244554"},"PeriodicalIF":0.0,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/fa/EMS185064.PMC7615016.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10197771","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}
Pub Date : 2023-08-03DOI: 10.3389/frnar.2023.1240954
E. Sparago, Reito Watanabe, J. Sharp, Michael D. Blower
During interphase, the nucleus contains a multitude of transcripts that influence the function of chromatin and global structure of the nucleus. Nuclear transcripts include nascent mRNAs in the process of transcription and mRNA processing, spliceosomal RNAs which catalyze mRNA processing, rRNAs that are being transcribed and processed to assemble functional ribosomes, and sno- and scaRNAs that participate in rRNA processing and modification. In addition, there are long noncoding RNAs (lncRNA) that associate with chromatin to control gene expression, or can even influence locus function in the case of centromeres and telomeres. Most of our knowledge of the functions of nuclear RNAs come from studies of interphase cells when the nuclear envelope separates nuclear and cytoplasmic contents. However, during mitosis the nuclear envelope breaks down, resulting in the mixing of nuclear and cytoplasmic components. Much less is known about the regulation and function of nuclear RNAs during mitosis. In this review, we discuss the cell cycle-dependent localization of different categories of RNAs, how the trans-acting factors SAF-A and Ki-67 regulate mitotic RNA localization, and describe how select categories of RNAs are inherited from the previous cell cycle in G1.
{"title":"Dynamic redistribution and inheritance of chromatin:RNA interactions during cell division","authors":"E. Sparago, Reito Watanabe, J. Sharp, Michael D. Blower","doi":"10.3389/frnar.2023.1240954","DOIUrl":"https://doi.org/10.3389/frnar.2023.1240954","url":null,"abstract":"During interphase, the nucleus contains a multitude of transcripts that influence the function of chromatin and global structure of the nucleus. Nuclear transcripts include nascent mRNAs in the process of transcription and mRNA processing, spliceosomal RNAs which catalyze mRNA processing, rRNAs that are being transcribed and processed to assemble functional ribosomes, and sno- and scaRNAs that participate in rRNA processing and modification. In addition, there are long noncoding RNAs (lncRNA) that associate with chromatin to control gene expression, or can even influence locus function in the case of centromeres and telomeres. Most of our knowledge of the functions of nuclear RNAs come from studies of interphase cells when the nuclear envelope separates nuclear and cytoplasmic contents. However, during mitosis the nuclear envelope breaks down, resulting in the mixing of nuclear and cytoplasmic components. Much less is known about the regulation and function of nuclear RNAs during mitosis. In this review, we discuss the cell cycle-dependent localization of different categories of RNAs, how the trans-acting factors SAF-A and Ki-67 regulate mitotic RNA localization, and describe how select categories of RNAs are inherited from the previous cell cycle in G1.","PeriodicalId":73105,"journal":{"name":"Frontiers in RNA research","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83709356","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}
Pub Date : 2023-06-05DOI: 10.3389/frnar.2023.1197990
Katheryn E. Lett, D. Mclaurin, Sara K. Tucker, M. Hebert
Cajal bodies (CBs) are subnuclear domains that contribute to the biogenesis of several different classes of ribonucleoproteins (RNPs), including small nuclear RNPs. Only some cell types contain abundant CBs, such as neuronal cells and skeletal muscle, but CBs are invariant features of transformed cells. In contrast, coilin, the CB marker protein, is a ubiquitously expressed nuclear protein, but the function of coilin in cell types that lack CBs is not well understood. We have previously shown that coilin promotes microRNA biogenesis by promoting phosphorylation of DGCR8, a component of the microprocessor. Here, we identify seven additional residues of DGCR8 with decreased phosphorylation upon coilin knockdown. In addition to phosphorylation, the addition of a small ubiquitin-like modifier (SUMO) to DGCR8 also increases its stability. Because of coilin’s role in the promotion of DGCR8 phosphorylation, we investigated whether coilin is involved in DGCR8 SUMOylation. We show that coilin knockdown results in global decrease of protein SUMOylation, including decreased DGCR8 and Sp100 (a PML body client protein) SUMOylation and decreased SMN expression. Alternatively, we found that coilin expression rescued Sp100 SUMOylation and increased DGCR8 and SMN levels in a coilin knockout cell line. Furthermore, we found that coilin facilitates RanGAP1 SUMOylation, interacts directly with components of the SUMOylation machinery (Ubc9 and SUMO2), and, itself, is SUMOylated in vitro and in vivo. In summary, we have identified coilin as a regulator of DGCR8 phosphorylation and a promotor of protein SUMOylation with SUMO E3 ligase-like activity.
{"title":"The Cajal body marker protein coilin is SUMOylated and possesses SUMO E3 ligase-like activity","authors":"Katheryn E. Lett, D. Mclaurin, Sara K. Tucker, M. Hebert","doi":"10.3389/frnar.2023.1197990","DOIUrl":"https://doi.org/10.3389/frnar.2023.1197990","url":null,"abstract":"Cajal bodies (CBs) are subnuclear domains that contribute to the biogenesis of several different classes of ribonucleoproteins (RNPs), including small nuclear RNPs. Only some cell types contain abundant CBs, such as neuronal cells and skeletal muscle, but CBs are invariant features of transformed cells. In contrast, coilin, the CB marker protein, is a ubiquitously expressed nuclear protein, but the function of coilin in cell types that lack CBs is not well understood. We have previously shown that coilin promotes microRNA biogenesis by promoting phosphorylation of DGCR8, a component of the microprocessor. Here, we identify seven additional residues of DGCR8 with decreased phosphorylation upon coilin knockdown. In addition to phosphorylation, the addition of a small ubiquitin-like modifier (SUMO) to DGCR8 also increases its stability. Because of coilin’s role in the promotion of DGCR8 phosphorylation, we investigated whether coilin is involved in DGCR8 SUMOylation. We show that coilin knockdown results in global decrease of protein SUMOylation, including decreased DGCR8 and Sp100 (a PML body client protein) SUMOylation and decreased SMN expression. Alternatively, we found that coilin expression rescued Sp100 SUMOylation and increased DGCR8 and SMN levels in a coilin knockout cell line. Furthermore, we found that coilin facilitates RanGAP1 SUMOylation, interacts directly with components of the SUMOylation machinery (Ubc9 and SUMO2), and, itself, is SUMOylated in vitro and in vivo. In summary, we have identified coilin as a regulator of DGCR8 phosphorylation and a promotor of protein SUMOylation with SUMO E3 ligase-like activity.","PeriodicalId":73105,"journal":{"name":"Frontiers in RNA research","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89340122","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}
Pub Date : 2023-06-01DOI: 10.3389/frnar.2023.1194526
J. Mattick
A longstanding enigma in molecular biology is the lack of scaling of protein-coding genes with developmental complexity, referred to as the g-value paradox. On the other hand, a feature of the evolution of multicellular organisms is the emergence of genetic loci termed “enhancers,” which control the spatiotemporal patterns of gene expression during development. Enhancer action has been widely interpreted in terms of an early model that postulated that transcription factors bound at enhancers are brought into juxtaposition with the promoters of target genes. This model tacitly assumed that there is no trans-acting gene product of enhancers, but subsequent studies have shown that enhancers are transcribed in the cells in which they are active. Like protein-coding genes, enhancers produce short bidirectional transcripts and long alternatively spliced RNAs, albeit at lower levels due to their transitory and cell-specific regulatory functions. The evidence indicates that long noncoding RNAs (lncRNAs) expressed from enhancers (elncRNAs) guide the formation of phase-separated transcriptional hubs and the epigenetic modifications to direct cell fate decisions during animal and plant ontogeny. Many, and likely most, lncRNAs are elncRNAs, which should be recognized as a bona fide class of gene products alongside mRNAs, rRNAs, tRNAs, snoRNAs, miRNAs and others of established function, with sequences specifying elncRNAs comprising an increasing fraction of genomic information as developmental complexity increases.
{"title":"Enhancers are genes that express organizational RNAs","authors":"J. Mattick","doi":"10.3389/frnar.2023.1194526","DOIUrl":"https://doi.org/10.3389/frnar.2023.1194526","url":null,"abstract":"A longstanding enigma in molecular biology is the lack of scaling of protein-coding genes with developmental complexity, referred to as the g-value paradox. On the other hand, a feature of the evolution of multicellular organisms is the emergence of genetic loci termed “enhancers,” which control the spatiotemporal patterns of gene expression during development. Enhancer action has been widely interpreted in terms of an early model that postulated that transcription factors bound at enhancers are brought into juxtaposition with the promoters of target genes. This model tacitly assumed that there is no trans-acting gene product of enhancers, but subsequent studies have shown that enhancers are transcribed in the cells in which they are active. Like protein-coding genes, enhancers produce short bidirectional transcripts and long alternatively spliced RNAs, albeit at lower levels due to their transitory and cell-specific regulatory functions. The evidence indicates that long noncoding RNAs (lncRNAs) expressed from enhancers (elncRNAs) guide the formation of phase-separated transcriptional hubs and the epigenetic modifications to direct cell fate decisions during animal and plant ontogeny. Many, and likely most, lncRNAs are elncRNAs, which should be recognized as a bona fide class of gene products alongside mRNAs, rRNAs, tRNAs, snoRNAs, miRNAs and others of established function, with sequences specifying elncRNAs comprising an increasing fraction of genomic information as developmental complexity increases.","PeriodicalId":73105,"journal":{"name":"Frontiers in RNA research","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85841741","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}
Pub Date : 2023-05-22DOI: 10.3389/frnar.2023.1152146
T. Gingeras
The biological importance of RNA has expanded as our appreciation of the complexity of its multiple types, structures, chemical compositions and biological roles. Research in RNA has been instrumental in revealing insights into fundamental biological processes including: the organization of information within genomes, the mechanisms of control of gene expression at the transcriptional (providing scaffolds for transcription factors and chromatin-modifying proteins) and post-transcriptional (RNA editing and modifications, translation, sponging) levels, spatiotemporal localization of elements involved in developmental and cell biology, and the evolution of first RNA genomes. Most recently, studies of RNA have expanded their clinical roles as diagnostics to the realm of therapeutic treatment for detected diseases. Finally, advances in RNA studies have been prompted by and contributed to the development of many novel methodological and computational approaches. The future of RNA research will add even more to our understanding of the origins of endophenotypes and these findings will be the focus of the Frontiers in RNA Research.
{"title":"Current frontiers in RNA research","authors":"T. Gingeras","doi":"10.3389/frnar.2023.1152146","DOIUrl":"https://doi.org/10.3389/frnar.2023.1152146","url":null,"abstract":"The biological importance of RNA has expanded as our appreciation of the complexity of its multiple types, structures, chemical compositions and biological roles. Research in RNA has been instrumental in revealing insights into fundamental biological processes including: the organization of information within genomes, the mechanisms of control of gene expression at the transcriptional (providing scaffolds for transcription factors and chromatin-modifying proteins) and post-transcriptional (RNA editing and modifications, translation, sponging) levels, spatiotemporal localization of elements involved in developmental and cell biology, and the evolution of first RNA genomes. Most recently, studies of RNA have expanded their clinical roles as diagnostics to the realm of therapeutic treatment for detected diseases. Finally, advances in RNA studies have been prompted by and contributed to the development of many novel methodological and computational approaches. The future of RNA research will add even more to our understanding of the origins of endophenotypes and these findings will be the focus of the Frontiers in RNA Research.","PeriodicalId":73105,"journal":{"name":"Frontiers in RNA research","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78820641","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}
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