Codon Usage and Splicing Jointly Influence mRNA Localization
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 characteriz...
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Published in | Cell systems Vol. 10; no. 4; pp. 351 - 362.e8 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
22.04.2020
Cell Press |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
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•Codon usage of human protein-coding genes is splicing- and position-dependent•Splicing enhances the expression of genes with low GC content•High GC content increases cytoplasmic mRNA localization•5′ terminal fusion of GC-rich sequences can be used to enhance expression
Mordstein et al. report an unexpected effect of splicing in human cells, whereby splicing preferentially enhances the expression of genes with low GC content. This might partially explain the high number of introns found in mammalian genomes. |
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Bibliography: | Lead Contact |
ISSN: | 2405-4712 2405-4720 |
DOI: | 10.1016/j.cels.2020.03.001 |