Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation.

Details

Serval ID
serval:BIB_ED9F802C1F1F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mammalian RNA Decay Pathways Are Highly Specialized and Widely Linked to Translation.
Journal
Molecular cell
Author(s)
Tuck A.C., Rankova A., Arpat A.B., Liechti L.A., Hess D., Iesmantavicius V., Castelo-Szekely V., Gatfield D., Bühler M.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Publication state
Published
Issued date
19/03/2020
Peer-reviewed
Oui
Volume
77
Number
6
Pages
1222-1236.e13
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
RNA decay is crucial for mRNA turnover and surveillance and misregulated in many diseases. This complex system is challenging to study, particularly in mammals, where it remains unclear whether decay pathways perform specialized versus redundant roles. Cytoplasmic pathways and links to translation are particularly enigmatic. By directly profiling decay factor targets and normal versus aberrant translation in mouse embryonic stem cells (mESCs), we uncovered extensive decay pathway specialization and crosstalk with translation. XRN1 (5'-3') mediates cytoplasmic bulk mRNA turnover whereas SKIV2L (3'-5') is universally recruited by ribosomes, tackling aberrant translation and sometimes modulating mRNA abundance. Further exploring translation surveillance revealed AVEN and FOCAD as SKIV2L interactors. AVEN prevents ribosome stalls at structured regions, which otherwise require SKIV2L for clearance. This pathway is crucial for histone translation, upstream open reading frame (uORF) regulation, and counteracting ribosome arrest on small ORFs. In summary, we uncovered key targets, components, and functions of mammalian RNA decay pathways and extensive coupling to translation.
Keywords
Animals, Apoptosis Regulatory Proteins/physiology, CRISPR-Cas Systems, DNA-Binding Proteins/physiology, Exoribonucleases/physiology, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mouse Embryonic Stem Cells/cytology, Mouse Embryonic Stem Cells/metabolism, Open Reading Frames, Protein Biosynthesis, Proto-Oncogene Proteins/physiology, RNA Helicases/physiology, RNA Stability, RNA, Messenger/chemistry, RNA, Messenger/genetics, RNA, Messenger/metabolism, Ribosomes/genetics, Ribosomes/metabolism, AVEN, RNA, RNA decay, RNA degradation, RNA surveillance, SKIV2L, histones, ribosome, ribosome stalling, translation
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / Projects / 51NF40_182880
Fondation Novartis
University of Lausanne
Swiss National Science Foundation / Projects / 31003A_179190
Create date
12/02/2020 14:08
Last modification date
25/07/2020 5:19
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