Translation is required for miRNA-dependent decay of endogenous transcripts.
Animals
Artificial Gene Fusion
Cell Line
Gene Expression Regulation
Genes, Reporter
High-Throughput Nucleotide Sequencing
Mice
MicroRNAs
/ genetics
Mouse Embryonic Stem Cells
/ cytology
Protein Biosynthesis
RNA Stability
RNA, Long Noncoding
/ genetics
RNA, Messenger
/ chemistry
Ribosomes
/ metabolism
Sequence Analysis, RNA
Dicer knockout mESC
RNA metabolic labelling
long noncoding RNAs
miRNA
translation
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
28
01
2020
revised:
30
10
2020
accepted:
06
11
2020
pubmed:
11
12
2020
medline:
5
10
2021
entrez:
10
12
2020
Statut:
ppublish
Résumé
Post-transcriptional repression of gene expression by miRNAs occurs through transcript destabilization or translation inhibition. mRNA decay is known to account for most miRNA-dependent repression. However, because transcript decay occurs co-translationally, whether target translation is a requirement for miRNA-dependent transcript destabilization remains unknown. To decouple these two molecular processes, we used cytosolic long noncoding RNAs (lncRNAs) as models for endogenous transcripts that are not translated. We show that, despite interacting with the miRNA-loaded RNA-induced silencing complex, the steady-state abundance and decay rates of these transcripts are minimally affected by miRNA loss. To further validate the apparent requirement of translation for miRNA-dependent decay, we fused two lncRNA candidates to the 3'-end of a protein-coding gene reporter and found this results in their miRNA-dependent destabilization. Further analysis revealed that the few natural lncRNAs whose levels are regulated by miRNAs in mESCs tend to associate with translating ribosomes, and possibly represent misannotated micropeptides, further substantiating the necessity of target translation for miRNA-dependent transcript decay. In summary, our analyses suggest that translation is required for miRNA-dependent transcript destabilization, and demonstrate that the levels of coding and noncoding transcripts are differently affected by miRNAs.
Identifiants
pubmed: 33300180
doi: 10.15252/embj.2020104569
pmc: PMC7849302
doi:
Substances chimiques
MicroRNAs
0
RNA, Long Noncoding
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e104569Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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