Mutations in spliceosomal proteins and retina degeneration

@article{Rzickov2017MutationsIS,
  title={Mutations in spliceosomal proteins and retina degeneration},
  author={S̆{\'a}rka Růz̆ic̆kov{\'a} and David Staněk},
  journal={RNA Biology},
  year={2017},
  volume={14},
  pages={544 - 552}
}
ABSTRACT A majority of human genes contain non-coding intervening sequences – introns that must be precisely excised from the pre-mRNA molecule. This event requires the coordinated action of five major small nuclear ribonucleoprotein particles (snRNPs) along with additional non-snRNP splicing proteins. Introns must be removed with nucleotidal precision, since even a single nucleotide mistake would result in a reading frame shift and production of a non-functional protein. Numerous human… 
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Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila
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Splicing mutations in inherited retinal diseases
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The data revealed that PRPF31 deficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on phototransduction and RNA processing.
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The current review focuses on the key RP-PRPF genes, depicting the current understanding of their roles in RNA splicing, impact of their mutations on retinal cell’s transcriptome and phenome, discussed in the context of model species including yeast, zebrafish, and mice.
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This study strongly suggests a role of DNAJC17 in splicing-related processes and provides support to its recognized essential function in early development.
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This is the first time that Prpf31 is demonstrated to be essential for the survival and differentiation of RPCs during retinal neurogenesis by specifically modulating the alternative splicing of genes involved in DNA repair and mitosis.
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TLDR
Using CRISPR in C. elegans, mutant strains to mimic RP mutations reported in PRPF8 and SNRNP200 are generated and it is found that snrp-200(cer23[V676L]) and prp-8(cer14[H2302del]) display pleiotropic phenotypes, but are weak alleles suitable for RNAi screens to identify genetic interactions, which would uncover potential disease modifiers.
Mimicking of splicing-related retinitis pigmentosa mutations in C. elegans allow drug screens and identification of disease modifiers.
TLDR
Using CRISPR in Caenorhabditis elegans, mutant strains are generated to mimic s-adRP mutations reported in PRPF8 and SNRNP200 and found that snrp-200(cer23[V676 L]) and prp-8(cer14[H2302del]) display pleiotropic phenotypes, but are weak alleles suitable for RNAi screens for identifying genetic interactions, which could uncover potential disease modifiers.
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