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.
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: | https://repository.cshl.edu/id/eprint/27441 |
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