Intact RNA structurome reveals mRNA structure-mediated regulation of miRNA cleavage in vivo.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
accepted:
24
06
2020
revised:
11
06
2020
received:
27
02
2020
pubmed:
12
7
2020
medline:
21
10
2020
entrez:
12
7
2020
Statut:
ppublish
Résumé
MicroRNA (miRNA)-mediated cleavage is involved in numerous essential cellular pathways. miRNAs recognize target RNAs via sequence complementarity. In addition to complementarity, in vitro and in silico studies have suggested that RNA structure may influence the accessibility of mRNAs to miRNA-induced silencing complexes (miRISCs), thereby affecting RNA silencing. However, the regulatory mechanism of mRNA structure in miRNA cleavage remains elusive. We investigated the role of in vivo RNA secondary structure in miRNA cleavage by developing the new CAP-STRUCTURE-seq method to capture the intact mRNA structurome in Arabidopsis thaliana. This approach revealed that miRNA target sites were not structurally accessible for miRISC binding prior to cleavage in vivo. Instead, we found that the unfolding of the target site structure plays a key role in miRISC activity in vivo. We found that the single-strandedness of the two nucleotides immediately downstream of the target site, named Target Adjacent nucleotide Motif, can promote miRNA cleavage but not miRNA binding, thus decoupling target site binding from cleavage. Our findings demonstrate that mRNA structure in vivo can modulate miRNA cleavage, providing evidence of mRNA structure-dependent regulation of biological processes.
Identifiants
pubmed: 32652041
pii: 5870339
doi: 10.1093/nar/gkaa577
pmc: PMC7470952
doi:
Substances chimiques
MicroRNAs
0
RNA Recognition Motif Proteins
0
RNA, Messenger
0
RNA-Induced Silencing Complex
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
8767-8781Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/J/000PR9788
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L025000/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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