A Depletion of Stop Codons in lincRNA is Owing to Transfer of Selective Constraint from Coding Sequences
Autor: | Liam Abrahams, Laurence D. Hurst |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
sequence evolution
ESE Biology Regulatory Sequences Ribonucleic Acid 03 medical and health sciences Exon transfer selection Open Reading Frames 0302 clinical medicine exonic splice enhancer Genetics stop codon Humans Selection Genetic Enhancer Molecular Biology Gene Ecology Evolution Behavior and Systematics Discoveries 030304 developmental biology 0303 health sciences Messenger RNA Models Genetic Intron Stop codon Open reading frame RNA splicing lincRNA Codon Terminator RNA Long Noncoding 030217 neurology & neurosurgery |
Zdroj: | Molecular Biology and Evolution |
ISSN: | 1537-1719 0737-4038 |
Popis: | Although the constraints on a gene’s sequence are often assumed to reflect the functioning of that gene, here we propose transfer selection, a constraint operating on one class of genes transferred to another, mediated by shared binding factors. We show that such transfer can explain an otherwise paradoxical depletion of stop codons in long intergenic noncoding RNAs (lincRNAs). Serine/arginine-rich proteins direct the splicing machinery by binding exonic splice enhancers (ESEs) in immature mRNA. As coding exons cannot contain stop codons in one reading frame, stop codons should be rare within ESEs. We confirm that the stop codon density (SCD) in ESE motifs is low, even accounting for nucleotide biases. Given that serine/arginine-rich proteins binding ESEs also facilitate lincRNA splicing, a low SCD could transfer to lincRNAs. As predicted, multiexon lincRNA exons are depleted in stop codons, a result not explained by open reading frame (ORF) contamination. Consistent with transfer selection, stop codon depletion in lincRNAs is most acute in exonic regions with the highest ESE density, disappears when ESEs are masked, is consistent with stop codon usage skews in ESEs, and is diminished in both single-exon lincRNAs and introns. Owing to low SCD, the maximum lengths of pseudo-ORFs frequently exceed null expectations. This has implications for ORF annotation and the evolution of de novo protein-coding genes from lincRNAs. We conclude that not all constraints operating on genes need be explained by the functioning of the gene but may instead be transferred owing to shared binding factors. |
Databáze: | OpenAIRE |
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