RNA helicases are essential for virtually all cellular processes, however, their regulation is poorly understood. The activities of eight RNA helicases are required for pre-mRNA splicing. Amongst these, Brr2p is unusual in having two helicase modules, of which only the amino-terminal helicase domain appears to be catalytically active. Using genetic and biochemical approaches, we investigated interaction of the carboxy-terminal helicase module, in particular the carboxy-terminal Sec63-2 domain, with the splicing RNA helicase Prp16p. Combining mutations in BRR2 and PRP16 suppresses or enhances physical interaction and growth defects in an allele-specific manner, signifying functional interactions. Notably, we show that Brr2p Sec63-2 domain can modulate the ATPase activity of Prp16p in vitro by interfering with its ability to bind RNA. We therefore propose that the carboxy-terminal helicase module of Brr2p acquired a regulatory function that allows Brr2p to modulate the ATPase activity of Prp16p in the spliceosome by controlling access to its RNA substrate/cofactor.
- School of Energy, Geoscience, Infrastructure and Society - Assistant Professor
- School of Energy, Geoscience, Infrastructure and Society, Institute for Life and Earth Sciences - Assistant Professor
Person: Academic (Research & Teaching)
Cordin, O., Hahn, D., Alexander, R., Gautum, A., Saveanu, C., Barrass, J. D., & Beggs, J. D. (2014). Brr2p carboxy-terminal Sec63 domain modulates Prp16 splicing RNA helicase. Nucleic Acids Research, 42(22), 13897-13910. https://doi.org/10.1093/nar/gku1238