Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
Keywords
Last Name
Institution

Contact Us
If you have any questions or feedback please contact us.

Structure and function of U5 snRNP


Collapse Biography 

Collapse Overview 
Collapse abstract
? DESCRIPTION (provided by applicant): Pre-mRNA splicing is essential for gene expression in all eukaryotes and errors in splicing cause genetic disorders and many other diseases. A thorough understanding of the molecular mechanisms of pre-mRNA splicing has the potential to provide useful approaches for human disease therapy. The splicing of introns is carried out through two transesterification reactions catalyzed by the spliceosome, a large RNA/protein complex composed of five snRNAs and over 100 protein factors. The five snRNAs (U1, U2, U4, U5, U6) and associated proteins form snRNPs, which play important roles in intron recognition, splice site definition, and the splicing reaction. U5 snRNP is a core spliceosomal component that contains U5 snRNA and three protein factors (Prp8, Brr2, and Snu114) that form a stable core even after chaotropic salt treatment. U5 snRNA interacts with both exons and is critical for aligning the exons for ligation in the second catalytic reaction. Prp8 lies in the heart of the spliceosome and is hypothesized to help form/stabilize the active site or even contribute functional groups to the catalytic reaction. Brr2 is a DExD/H-box protein responsible for U4/U6 unwinding, an essential step for spliceosomal activation. Snu114 is the only GTPase in the spliceosome and is thought to regulate the activity of Brr2. Crystal structures of several domains of Prp8 and Brr2 are known, but there is no structure of any full-length protein or U5 snRNA. It is not clear how proteins in U5 snRNP interact with each other, with U5 snRNA, or with the spliceosome catalytic core. The goal of this proposal is to determine the structure and function of components of the U5 snRNP, as well as their complexes with other proteins and RNAs (including those at the spliceosome catalytic core), using a combination of cutting edge cryo-electron microscopy, crystallography, biochemistry, and yeast genetics approaches. A thorough understanding of the structure and function of U5 snRNP will significantly advance our understanding of the molecular mechanisms of pre-mRNA splicing in general.
Collapse sponsor award id
R01GM114178

Collapse Time 
Collapse start date
2015-04-01
Collapse end date
2020-03-31

Copyright © 2022 The Regents of the University of Colorado, a body corporate. All rights reserved. (Harvard PROFILES RNS software version: 2.11.1)