AI Article Synopsis
- Recurrent mutations in the spliceosome, particularly in the SF3B1 component, are linked to several human cancers but their exact roles in cancer progression and treatment are not fully understood.
- SF3B1 mutations lead to common and tumor-specific splicing defects, primarily causing abnormal selection of the 3' splice sites, which impacts RNA splicing accuracy.
- Around 50% of mRNAs affected by these splicing errors are targeted for decay, resulting in reduced gene and protein expression, highlighting the functional importance of SF3B1 mutations in cancer.
Article Abstract
Recurrent mutations in the spliceosome are observed in several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3' splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3' ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3' ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer.
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| http://dx.doi.org/10.1016/j.celrep.2015.09.053 | DOI Listing |
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