SNRP-27, the C. elegans homolog of the tri-snRNP 27K protein, has a role in 5' splice site positioning in the spliceosome

RNA
Alan M ZahlerSol Katzman

Abstract

The tri-snRNP 27K protein is a component of the human U4/U6-U5 tri-snRNP and contains an N-terminal phosphorylated RS domain. In a forward genetic screen in C. elegans, we previously identified a dominant mutation, M141T, in the highly-conserved C-terminal region of this protein. The mutant allele promotes changes in cryptic 5' splice site choice. To better understand the function of this poorly characterized splicing factor, we performed high-throughput mRNA sequencing analysis on worms containing this dominant mutation. Comparison of alternative splice site usage between the mutant and wild-type strains led to the identification of 26 native genes whose splicing changes in the presence of the snrp-27 mutation. The changes in splicing are specific to alternative 5' splice sites. Analysis of new alleles suggests that snrp-27 is an essential gene for worm viability. We performed a novel directed-mutation experiment in which we used the CRISPR-cas9 system to randomly generate mutations specifically at M141 of SNRP-27. We identified eight amino acid substitutions at this position that are viable, and three that are homozygous lethal. All viable substitutions at M141 led to varying degrees of changes in alternative 5' splicing of n...Continue Reading

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Citations

Jul 8, 2020·Genetics·Joshua A ArribereHeather A Hundley
Apr 13, 2019·Science·Clément CharentonKiyoshi Nagai
Jan 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Megan MayerleAlan M Zahler
Jul 28, 2020·Current Opinion in Structural Biology·Sebastian M Fica
Jun 3, 2021·International Journal of Molecular Sciences·Maxime BlijlevensVictor W van Beusechem
Aug 5, 2021·Cell Reports·Bikash ChoudharyAdam D Norris

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