Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA

Roca, X., Krainer, A. R. (February 2009) Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA. Nat Struct Mol Biol, 16 (2). pp. 176-182.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19169258
DOI: 10.1038/nsmb.1546

Abstract

Accurate pre-mRNA splicing is crucial for gene expression. The 5' splice site (5' ss)—the highly diverse element at the 5' end of introns—is initially recognized via base-pairing to the 5' end of the U1 small nuclear RNA (snRNA). However, many natural 5' ss have a poor match to the consensus sequence, and are predicted to be weak. Using genetic suppression experiments in human cells, we demonstrate that some atypical 5' ss are actually efficiently recognized by U1, in an alternative base-pairing register that is shifted by one nucleotide. These atypical 5' ss are phylogenetically widespread, and many of them are conserved. Moreover, shifted base-pairing provides an explanation for the effect of a 5' ss mutation associated with pontocerebellar hypoplasia. The unexpected flexibility in 5' ss–U1 base-pairing challenges an established paradigm and has broad implications for splice-site prediction algorithms and gene-annotation efforts in genome projects.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > snRNA
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: February 2009
Date Deposited: 19 Feb 2013 21:35
Last Modified: 19 Feb 2013 21:35
PMCID: PMC2719486
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27441

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