Codon Usage and Splicing Jointly Influence mRNA Localization.

Cell Systems
Christine MordsteinGrzegorz Kudla

Abstract

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.

Citations

Nov 10, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alexander F Palazzo, Yoon Mo Kang
Dec 15, 2020·Wellcome Open Research·Stefan BressonDavid Tollervey
Jan 8, 2021·Nucleic Acids Research·Qian YangYi Liu
Jan 7, 2021·MBio·Daniel Gonçalves-Carneiro, Paul D Bieniasz
Nov 1, 2020·Cellular and Molecular Life Sciences : CMLS·Fabian Hia, Osamu Takeuchi
Oct 18, 2020·Cell·Alexander F Palazzo, Eugene V Koonin
Apr 20, 2021·Molecular Biology and Evolution·Janaina Lima de OliveiraJason B Wolf
Jun 4, 2021·Frontiers in Cardiovascular Medicine·David R SweetMukesh K Jain
Jan 15, 2021·Annual Review of Biochemistry·Yi LiuFangzhou Zhao
Jun 23, 2021·Wiley Interdisciplinary Reviews. RNA·Eleanor R Gaunt, Paul Digard
May 15, 2021·Genome Biology and Evolution·Christine MordsteinGrzegorz Kudla
Sep 7, 2021·Immunological Reviews·Benoit P NicoletMonika C Wolkers

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Datasets Mentioned

BETA
PRJNA596086

Methods Mentioned

BETA
transfection
transfections
Flow-seq
fluorescence-activated
amplicon sequencing
FACS
protein folding
RNA-seq
PCR
light microscopy

Software Mentioned

Kallisto
Ensembl
corrplot
seqinr
DESeq2
Flow
ss
bowtie2
R Development Core
GENCODE

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