Codon Usage and Splicing Jointly Influence mRNA Localization.
Active Transport, Cell Nucleus
/ genetics
Alternative Splicing
/ genetics
Base Composition
/ genetics
Codon
/ genetics
Codon Usage
/ genetics
Exons
/ genetics
Gene Expression
/ genetics
Genome, Human
/ genetics
HEK293 Cells
HeLa Cells
Humans
RNA Splicing
/ genetics
RNA Transport
/ genetics
RNA, Messenger
/ genetics
codon usage
evolution
mRNA export
saturation mutagenesis
splicing
synthetic biology
Journal
Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080
Informations de publication
Date de publication:
22 04 2020
22 04 2020
Historique:
received:
04
02
2019
revised:
19
12
2019
accepted:
05
03
2020
pubmed:
11
4
2020
medline:
7
7
2021
entrez:
11
4
2020
Statut:
ppublish
Résumé
In the human genome, most genes undergo splicing, and patterns of codon usage are splicing dependent: guanine and cytosine (GC) content is the highest within single-exon genes and within first exons of multi-exon genes. However, the effects of codon usage on gene expression are typically characterized in unspliced model genes. Here, we measured the effects of splicing on expression in a panel of synonymous reporter genes that varied in nucleotide composition. We found that high GC content increased protein yield, mRNA yield, cytoplasmic mRNA localization, and translation of unspliced reporters. Splicing did not affect the expression of GC-rich variants. However, splicing promoted the expression of AT-rich variants by increasing their steady-state protein and mRNA levels, in part through promoting cytoplasmic localization of mRNA. We propose that splicing promotes the nuclear export of AU-rich mRNAs and that codon- and splicing-dependent effects on expression are under evolutionary pressure in the human genome.
Identifiants
pubmed: 32275854
pii: S2405-4712(20)30080-6
doi: 10.1016/j.cels.2020.03.001
pmc: PMC7181179
pii:
doi:
Substances chimiques
Codon
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
351-362.e8Subventions
Organisme : Medical Research Council
ID : MC_UU_00007/12
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/11
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 207507
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 097383
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 097383
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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