Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA
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...
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| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
2011
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/91923 http://hdl.handle.net/10220/6872 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | 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. |
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