Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Kornblihtt, Alberto R.
Location University of Buenos Aires
Primary Field Biochemistry
Secondary Field Genetics
 Election Citation
Kornblihtt made fundamental contributions on the mechanisms regulating alternative pre-mRNA splicing. Most importantly, he showed that promoter-specific differences in transcriptional elongation rates and the recruitment of splicing factors to the RNA polymerase profoundly affect alternative splicing and, therefore, the generation of multiple protein variants from a single gene.
 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.

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