Quantitative Activity Profile and Context Dependence of All Human 5' Splice Sites

Wong, M. S., Kinney, J. B., Krainer, A. R. (August 2018) Quantitative Activity Profile and Context Dependence of All Human 5' Splice Sites. Mol Cell, 71 (6). 1012-1026.e3. ISSN 1097-2765

URL: https://www.ncbi.nlm.nih.gov/pubmed/30174293
DOI: 10.1016/j.molcel.2018.07.033

Abstract

Pre-mRNA splicing is an essential step in the expression of most human genes. Mutations at the 5' splice site (5'ss) frequently cause defective splicing and disease due to interference with the initial recognition of the exon-intron boundary by U1 small nuclear ribonucleoprotein (snRNP), a component of the spliceosome. Here, we use a massively parallel splicing assay (MPSA) in human cells to quantify the activity of all 32,768 unique 5'ss sequences (NNN/GYNNNN) in three different gene contexts. Our results reveal that although splicing efficiency is mostly governed by the 5'ss sequence, there are substantial differences in this efficiency across gene contexts. Among other uses, these MPSA measurements facilitate the prediction of 5'ss sequence variants that are likely to cause aberrant splicing. This approach provides a framework to assess potential pathogenic variants in the human genome and streamline the development of splicing-corrective therapies.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Alternative Splicing
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 > splice site
CSHL Authors:
Communities: CSHL labs > Kinney lab
CSHL labs > Krainer lab
Depositing User: Matthew Dunn
Date: 16 August 2018
Date Deposited: 05 Sep 2018 13:33
Last Modified: 23 Apr 2019 14:54
PMCID: PMC6179149
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37180

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving