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

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

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dc.contributor.author Roca, Xavier
dc.contributor.author Krainer, Adrian R.
dc.date.accessioned 2011-07-06T04:42:05Z
dc.date.available 2011-07-06T04:42:05Z
dc.date.copyright 2009
dc.date.issued 2011-07-06T04:42:05Z
dc.identifier.citation Roca, X., & Krainer, A. R. (2009). Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA. Nature Structural and Molecular Biology, 16, 176-182.
dc.identifier.uri http://hdl.handle.net/10220/6872
dc.description.abstract Accurate pre-mRNA splicing is critical 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 U1 small nuclear RNA (snRNA). However, many natural 5' ss have a very poor match to the consensus sequence, and are predicted to be very 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.
dc.format.extent 19 p.
dc.language.iso en
dc.relation.ispartofseries Nature structural and molecular Biology
dc.rights © 2009 Nature Publishing Group. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature Structural and Molecular Biology, Nature Publishing Group. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: http://dx.doi.org/10.1038/nsmb.1546.
dc.subject DRNTU::Science::Biological sciences::Molecular biology.
dc.title Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA
dc.type Journal Article
dc.contributor.school School of Biological Sciences
dc.identifier.doi http://dx.doi.org/10.1038/nsmb.1546
dc.description.version Accepted version

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