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
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 CSHL Cancer Center Program > Gene Regulation and Inheritance Program |
| Depositing User: | Matthew Dunn |
| Date: | 16 August 2018 |
| Date Deposited: | 05 Sep 2018 13:33 |
| Last Modified: | 26 Oct 2020 20:39 |
| PMCID: | PMC6179149 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37180 |
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