Alberto R. Kornblihtt
University of Buenos Aires
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Primary Section: 21, Biochemistry Secondary Section: 26, Genetics Membership Type:
International Member
(elected 2011)
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Research Interests
As a molecular biologist, I have studied the regulation of alternative pre-mRNA splicing, the mechanism that explains how every single human gene generates multiple proteins. My lab proved that promoters affect alternative splicing, a finding that changed the classical view of splicing as a transcription-independent process, indicating, on the contrary, that splicing and transcription are functionally coupled. We demonstrated that the coupling occurs through two non-mutually exclusive mechanisms: the control of transcriptional elongation speed (kinetic coupling), and the association of splicing factors to RNA polymerase II (recruitment coupling), the enzyme in charge of transcribing the genes. We also found that DNA damage caused by UV irradiation affects alternative splicing by causing a reduction in RNA polymerase II elongation, confirming the physiological importance of the coupling. My lab also discovered that changes in chromatin structure and histone post-translational modifications modulate alternative splicing, and that small noncoding RNAs can regulate alternative splicing by affecting chromatin structure, which contributed to the rising field of the relationship between epigenetics and splicing.
