Title
Activation of Prp28 ATPase by Phosphorylated Npl3 at a Critical Step of Spliceosome Remodeling
Document Type
Article
Publication Date
12-2021
Abstract
Splicing, a key step in the eukaryotic gene-expression pathway, converts precursor messenger RNA (pre-mRNA) into mRNA by excising introns and ligating exons. This task is accomplished by the spliceosome, a macromolecular machine that must undergo sequential conformational changes to establish its active site. Each of these major changes requires a dedicated DExD/H-box ATPase, but how these enzymes are activated remain obscure. Here we show that Prp28, a yeast DEAD-box ATPase, transiently interacts with the conserved 5' splice-site (5'SS) GU dinucleotide and makes splicing-dependent contacts with the U1 snRNP protein U1C, and U4/U6.U5 tri-snRNP proteins, Prp8, Brr2, and Snu114. We further show that Prp28's ATPase activity is potentiated by the phosphorylated Npl3, but not the unphosphorylated Npl3, thus suggesting a strategy for regulating DExD/H-box ATPases. We propose that Npl3 is a functional counterpart of the metazoan-specific Prp28 N-terminal region, which can be phosphorylated and serves as an anchor to human spliceosome.
Identifier
PMID: 34035302
DOI
10.1038/s41467-021-23459-4
Publisher
Springer Nature
Repository Citation
Yeh, F.-L., Chang, S.-L., Ahmed, G. R., Liu, H.-I., Tung, L., Yeh, C.-S., Lanier, L. S., ... & Chang, T.-H. (2021). Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling. Nature Communications, 12(1), Article 3082. https://doi.org/10.1038/s41467-021-23459-4
Publication Information
Nature Communications