Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
20 09 2023
Historique:
received: 23 08 2022
accepted: 08 09 2023
medline: 22 9 2023
pubmed: 21 9 2023
entrez: 20 9 2023
Statut: epublish

Résumé

The transcriptional intermediates of RNAs fold into secondary structures with multiple regulatory roles, yet the details of such cotranscriptional RNA folding are largely unresolved in eukaryotes. Here, we present eSPET-seq (Structural Probing of Elongating Transcripts in eukaryotes), a method to assess the cotranscriptional RNA folding in Saccharomyces cerevisiae. Our study reveals pervasive structural transitions during cotranscriptional folding and overall structural similarities between nascent and mature RNAs. Furthermore, a combined analysis with genome-wide R-loop and mutation rate approximations provides quantitative evidence for the antimutator effect of nascent RNA folding through competitive inhibition of the R-loops, known to facilitate transcription-associated mutagenesis. Taken together, we present an experimental evaluation of cotranscriptional folding in eukaryotes and demonstrate the antimutator effect of nascent RNA folding. These results suggest genome-wide coupling between the processing and transmission of genetic information through RNA folding.

Identifiants

pubmed: 37730811
doi: 10.1038/s41467-023-41550-w
pii: 10.1038/s41467-023-41550-w
pmc: PMC10511511
doi:

Substances chimiques

Antimutagenic Agents 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5853

Informations de copyright

© 2023. Springer Nature Limited.

Références

Nat Protoc. 2015 Jul;10(7):1050-66
pubmed: 26086407
Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):839-43
pubmed: 1992475
Nat Rev Mol Cell Biol. 2007 Feb;8(2):113-26
pubmed: 17245413
Nature. 2015 Mar 26;519(7544):486-90
pubmed: 25799993
Genome Biol Evol. 2011;3:1107-18
pubmed: 21821597
Cancer Res. 1991 Jun 15;51(12):3075-9
pubmed: 2039987
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
Nat Rev Genet. 2015 Jul;16(7):409-20
pubmed: 26055156
Trends Genet. 2002 Jul;18(7):337-40
pubmed: 12127766
Genome. 1989;31(1):24-31
pubmed: 2687096
Mol Cell. 2021 Apr 15;81(8):1789-1801.e5
pubmed: 33631106
Curr Opin Genet Dev. 2003 Dec;13(6):562-8
pubmed: 14638315
Mol Cell. 2010 Nov 24;40(4):571-81
pubmed: 21095587
Nature. 2006 Jan 26;439(7075):497-501
pubmed: 16299494
Nat Genet. 2016 Apr;48(4):349-55
pubmed: 26878723
Mol Biol Evol. 2017 Oct 1;34(10):2486-2502
pubmed: 28472365
Cell. 1999 Sep 17;98(6):799-810
pubmed: 10499797
Trends Cell Biol. 2021 May;31(5):359-371
pubmed: 33685798
Bioinformatics. 2023 Jan 1;39(1):
pubmed: 36655786
Proc Natl Acad Sci U S A. 1986 Dec;83(23):8878-82
pubmed: 3466163
Genome Biol. 2013 Feb 14;14(2):R13
pubmed: 23409723
Trends Biochem Sci. 2010 Mar;35(3):169-78
pubmed: 19959365
Genome Res. 2009 Jul;19(7):1195-201
pubmed: 19439516
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Nature. 2014 Jan 30;505(7485):696-700
pubmed: 24270811
Curr Biol. 2019 May 20;29(10):1584-1591.e3
pubmed: 31056389
J Mol Evol. 1997;44 Suppl 1:S139-46
pubmed: 9071022
Mol Biol Evol. 1997 Nov;14(11):1106-13
pubmed: 9364768
Cell. 2018 Mar 22;173(1):181-195.e18
pubmed: 29551268
Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):E4062
pubmed: 25217566
Biochemistry. 1995 Aug 29;34(34):10807-15
pubmed: 7662660
Mol Biol Evol. 2020 Nov 1;37(11):3225-3231
pubmed: 32638015
Nature. 2014 Jan 30;505(7485):701-5
pubmed: 24336214
Annu Rev Genet. 2002;36:279-303
pubmed: 12429694
Nature. 2014 Jan 30;505(7485):706-9
pubmed: 24476892
Nat Ecol Evol. 2022 Jan;6(1):103-115
pubmed: 34795386
Genome Res. 2018 Jul;28(7):1008-1019
pubmed: 29903723
Science. 2008 Jun 6;320(5881):1344-9
pubmed: 18451266
PLoS Genet. 2013;9(1):e1003176
pubmed: 23300483
Nat Protoc. 2016 Feb;11(2):273-90
pubmed: 26766114
PLoS Biol. 2014 Jul 22;12(7):e1001910
pubmed: 25051069
Genome Res. 2016 Jan;26(1):50-9
pubmed: 26518484
Nat Commun. 2023 Sep 20;14(1):5853
pubmed: 37730811
Methods. 2016 Jul 1;103:86-98
pubmed: 27064083
Bioorg Med Chem. 1997 Jun;5(6):1197-207
pubmed: 9222513
Genes Dev. 2016 Jun 1;30(11):1327-38
pubmed: 27298336
Genetics. 2004 Sep;168(1):373-81
pubmed: 15454550
Nat Struct Mol Biol. 2019 Apr;26(4):322-330
pubmed: 30886404
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E678-86
pubmed: 23382244
PLoS Genet. 2014 Oct 30;10(10):e1004716
pubmed: 25357144
Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):E2310-8
pubmed: 24847077
Annu Rev Biophys Biomol Struct. 2006;35:161-75
pubmed: 16689632
Biophys J. 2003 Jan;84(1):432-9
pubmed: 12524296
Annu Rev Genet. 2014;48:341-59
pubmed: 25251854
Genetics. 2002 Apr;160(4):1409-22
pubmed: 11973297
PLoS Genet. 2008 Aug 29;4(8):e1000183
pubmed: 18769710
Nature. 2010 Sep 2;467(7311):103-7
pubmed: 20811459
Nature. 2011 Jan 20;469(7330):368-73
pubmed: 21248844
Nucleic Acids Res. 2017 Sep 19;45(16):9716-9725
pubmed: 28934475
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8948-53
pubmed: 22615360
RNA Biol. 2011 May-Jun;8(3):450-7
pubmed: 21558794
Cell. 2016 May 19;165(5):1267-1279
pubmed: 27180905
J Biol Chem. 2020 Jan 24;295(4):905-913
pubmed: 31843970
Nat Methods. 2017 Jan;14(1):75-82
pubmed: 27819661
Genetics. 1989 Nov;123(3):585-95
pubmed: 2513255
Genome Biol. 2014;15(10):491
pubmed: 25323333
Cell. 2016 Apr 7;165(2):372-381
pubmed: 27020755
Nat Rev Genet. 2016 Oct 14;17(11):704-714
pubmed: 27739533
Nature. 2015 May 7;521(7550):81-4
pubmed: 25707793

Auteurs

Gongwang Yu (G)

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Yao Liu (Y)

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Zizhang Li (Z)

Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Shuyun Deng (S)

Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Zhuoxing Wu (Z)

Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Xiaoyu Zhang (X)

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Wenbo Chen (W)

Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Junnan Yang (J)

Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Xiaoshu Chen (X)

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China.

Jian-Rong Yang (JR)

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. yangjianrong@mail.sysu.edu.cn.
Department of Genetics and Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. yangjianrong@mail.sysu.edu.cn.
Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China. yangjianrong@mail.sysu.edu.cn.

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Classifications MeSH