Flemr et al. 2023 (PRJNA744888)

Title	Novel RNA-binding Proteins Bind U1 snRNA to Promote Splicing of Weak 5' Splice Sites
Organism
Number of Samples	4
Release Date	2021/07/08 00:00
Sequencing Types
Protocol Details

GWIPS-viz	Trips-Viz

Title
Authors	Flemr M,Schwaiger M,Hess D,Iesmantavicius V,Ahel J,Tuck AC,Mohn F,Bühler M
Journal	RNA (New York, N.Y.)
Publication Date	2023 Aug
Abstract	Removal of introns during pre-mRNA splicing, which is central to gene expression, initiates by base pairing of U1 snRNA with a 5' splice site (5'SS). In mammals, many introns contain weak 5'SSs that are not efficiently recognized by the canonical U1 snRNP, suggesting alternative mechanisms exist. Here, we develop a cross-linking immunoprecipitation coupled to a high-throughput sequencing method, BCLIP-seq, to identify NRDE2 (nuclear RNAi-defective 2), and CCDC174 (coiled-coil domain-containing 174) as novel RNA-binding proteins in mouse ES cells that associate with U1 snRNA and 5'SSs. Both proteins bind directly to U1 snRNA independently of canonical U1 snRNP-specific proteins, and they are required for the selection and effective processing of weak 5'SSs. Our results reveal that mammalian cells use noncanonical splicing factors bound directly to U1 snRNA to effectively select suboptimal 5'SS sequences in hundreds of genes, promoting proper splice site choice, and accurate pre-mRNA splicing. © 2023 Flemr et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
PMC	PMC10351895
PMID	37137667
DOI

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