Allele-specific alternative splicing of Drosophila Ribosomal protein S21 suppresses a lethal mutation in the Phosphorylated adaptor for RNA export (Phax) gene.

Eric L Garcia

G3 (Bethesda, Md.) 2022 Aug 25

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Genetic disruptions to the biogenesis of spliceosomal small-nuclear ribonucleoproteins in Drosophila cause wide-spread alternative splicing changes, including changes to the splicing of pre-mRNA for Ribosomal protein S21 (RpS21). Using a transposon mutant for the Phosphorylated adaptor for RNA export (Phax) gene, we demonstrate that changes in the splicing of RpS21 transcripts have a strong influence on the developmental progression of PhaxSH/SH mutants. Different alleles of the Drosophila RpS21 gene are circulating in common laboratory strains and cell lines. These alleles exhibit differences in RpS21 intron retention and splicing efficiency. Differences in the splicing of RpS21 transcripts account for prior conflicting observations of the phenotypic severity of PhaxSH/SH mutant stocks. The alleles uncover a strong splicing enhancer in RpS21 transcripts that can fully suppress the larval lethality and partially suppress the pupal lethality exhibited by PhaxSH/SH mutant lines. In the absence of the splicing enhancer, the splicing of RpS21 transcripts can be modulated in trans by the SR-rich B52 splicing factor. As PhaxSH/SH mutants exhibit wide-spread splicing changes in transcripts for other genes, findings here establish the importance of a single alternative splicing event, RpS21 splicing or intron retention, to the developmental progression of Drosophila. © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.

Citation

Eric L Garcia. Allele-specific alternative splicing of Drosophila Ribosomal protein S21 suppresses a lethal mutation in the Phosphorylated adaptor for RNA export (Phax) gene. G3 (Bethesda, Md.). 2022 Aug 25;12(9)