Codon Usage and Splicing Jointly Influence mRNA Localization
| Autor: | Grzegorz Kudla, Rosina Savisaar, Lana Talmane, Christine Mordstein, Jeanne Bazile, Martin S. Taylor, Laurence D. Hurst, Michael Liss, Robert Young, Juliet Luft |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Histology
RNA Splicing Active Transport Cell Nucleus Gene Expression saturation mutagenesis Biology RNA Transport Article Pathology and Forensic Medicine 03 medical and health sciences Exon splicing 0302 clinical medicine Gene expression evolution Humans RNA Messenger Codon Gene 030304 developmental biology Genetics mRNA export 0303 health sciences Messenger RNA Base Composition codon usage Genome Human Cell Biology Exons Alternative Splicing HEK293 Cells Codon usage bias RNA splicing Human genome synthetic biology 030217 neurology & neurosurgery GC-content HeLa Cells |
| Zdroj: | Mordstein, C, Savisaar, R, Young, R S, Bazile, J, Talmane, L, Luft, J, Liss, M, Taylor, M S, Hurst, L D & Kudla, G 2020, ' Codon Usage and Splicing Jointly Influence mRNA Localization ', Cell Systems, vol. 10, no. 4, pp. 351-362.e8 . https://doi.org/10.1016/j.cels.2020.03.001 Cell Systems |
| DOI: | 10.1016/j.cels.2020.03.001 |
| Popis: | 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. Graphical Abstract Highlights • 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. |
| Databáze: | OpenAIRE |
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