Mutated Cohesin Throws DNA Splicing out of Whack, Resulting in Cancer

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"... A study ... suggests that cohesin regulates alternative splicing—the phenomenon when coding regions of a gene are combined in different ways during transcription, allowing the gene to code for multiple distinct proteins —which is important for a range of cellular processes, including cell development and death. This also implicates cohesin in the development of acute myeloid leukemia (AML) and other types of cancer, which can grow and progress when alternative splicing runs rampant. ..."

From the abstract:

"Cohesin, a trimeric complex that establishes sister chromatid cohesion, has additional roles in chromatin organization and transcription. We report that among those roles is the regulation of alternative splicing through direct interactions and in situ colocalization with splicing factors. Degradation of cohesin results in marked changes in splicing, independent of its effects on transcription. Introduction of a single cohesin point mutation in embryonic stem cells alters splicing patterns, demonstrating causality. In primary human acute myeloid leukemia, mutations in cohesin are highly correlated with distinct patterns of alternative splicing. Cohesin also directly interacts with BRD4, another splicing regulator, to generate a pattern of splicing that is distinct from either factor alone, documenting their functional interaction. These findings identify a role for cohesin in regulating alternative splicing in both normal and leukemic cells and provide insights into the role of cohesin mutations in human disease."

"... Cohesin mutations are frequently observed in a variety of different diseases. Among the diseases where cohesin mutations have been found is acute myeloid leukemia (AML), where mutations in cohesin components occur at a frequency of up to 20% ..."

Mutated Cohesin Throws DNA Splicing out of Whack, Resulting in Cancer | The Scientist Magazine® Cohesin mutations cause dysregulations in alternative splicing, contributing to tumor initiation and progression, a study finds. 

Cohesin regulates alternative splicing (open access)

Fig. 6. Cohesin mutations correlate with changes in alternative splicing in patients with AML.