Prp8 positioning of U5 snRNA is linked to 5' splice site recognition

RNA
Andrew J MacRaeMelissa S Jurica

Abstract

Prp8 is an essential protein that regulates spliceosome assembly and conformation during pre-mRNA splicing. Recent cryo-EM structures of the spliceosome model Prp8 as a scaffold for the spliceosome's catalytic U snRNA components. Using a new amino acid probing strategy, we identified a dynamic region in human Prp8 that is positioned to stabilize the pre-mRNA in the spliceosome active site through interactions with U5 snRNA. Mutagenesis of the identified Prp8 residues in yeast indicates a role in 5' splice site recognition. Genetic interactions with spliceosome proteins Isy1, which buttresses the intron branch point, and Snu114, a regulatory GTPase that directly contacts Prp8, further corroborate a role for the same Prp8 residues in substrate positioning and activation. Together the data suggest that adjustments in interactions between Prp8 and U5 snRNA help establish proper positioning of the pre-mRNA into the active site to enhance 5' splice site fidelity.

References

Oct 28, 2004·Biochemical Society Transactions·I A TurnerA J Newman
Jan 13, 2006·Methods in Enzymology·Robert J ChalkleyMichael A Baldwin
May 9, 2007·Nature Structural & Molecular Biology·Li LiuMaria M Konarska
Jul 28, 2016·Nature·Wojciech P GalejKiyoshi Nagai
Jan 12, 2017·Nature·Sebastian M FicaKiyoshi Nagai
Jan 12, 2017·Nature·Karl BertramReinhard Lührmann
May 16, 2017·Cell·Xiaofeng ZhangYigong Shi
May 23, 2017·Nature·Clemens PlaschkaKiyoshi Nagai

❮ Previous
Next ❯

Citations

Jan 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Megan MayerleAlan M Zahler
Sep 2, 2020·Annual Review of Genetics·Erin K BorchardtWendy V Gilbert
Jan 20, 2021·Chemosphere·Jialu BaoXiaodan Wang
Aug 8, 2021·International Journal of Molecular Sciences·Naoyuki KataokaSo Masaki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.