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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Roca, Xavier Akerman, Martin Gaus, Hans Berdeja, Andrés Bennett, C. Frank Krainer, Adrian R. |
| Description | Country affiliation: United States Author Affiliation: Roca X ( Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.) |
| Abstract | An established paradigm in pre-mRNA splicing is the recognition of the 5' splice site (5'ss) by canonical base-pairing to the 5' end of U1 small nuclear RNA (snRNA). We recently reported that a small subset of 5'ss base-pair to U1 in an alternate register that is shifted by 1 nucleotide. Using genetic suppression experiments in human cells, we now demonstrate that many other 5'ss are recognized via noncanonical base-pairing registers involving bulged nucleotides on either the 5'ss or U1 RNA strand, which we term 'bulge registers.' By combining experimental evidence with transcriptome-wide free-energy calculations of 5'ss/U1 base-pairing, we estimate that 10,248 5'ss (â¼5% of human 5'ss) in 6577 genes use bulge registers. Several of these 5'ss occur in genes with mutations causing genetic diseases and are often associated with alternative splicing. These results call for a redefinition of an essential element for gene expression that incorporates these registers, with important implications for the molecular classification of splicing mutations and for alternative splicing. |
| File Format | HTM / HTML |
| ISSN | 08909369 |
| e-ISSN | 15495477 |
| DOI | 10.1101/gad.190173.112 |
| Journal | Genes & Development |
| Issue Number | 10 |
| Volume Number | 26 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2012-05-15 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Alternative Splicing Base Pairing Rna Splice Sites Genetics Rna, Small Nuclear Chemistry Ribonucleotides Hela Cells Nucleic Acid Conformation Transcriptome Research Support, N.i.h., Extramural |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Developmental Biology |
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