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PMID: 23727230 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site.

Structure (London, England : 1993) ·Vol. 21 ·No. 6 ·2013-06-04 ·Pages 910-19

Nguyen TH, Li J, Galej WP, Oshikane H, Newman AJ, Nagai K

Abstract

The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Smproteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP.

MeSH Terms
Catalytic Domain Mutation Protein Binding Protein Conformation RNA Helicases/chemistry,metabolism RNA, Small Nuclear/metabolism RNA-Binding Proteins/chemistry,genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,metabolism Spliceosomes
Chemicals
PRPF8 protein, human RNA, Small Nuclear RNA-Binding Proteins Saccharomyces cerevisiae Proteins U5 small nuclear RNA BRR2 protein, S cerevisiae RNA Helicases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nguyen Thi Hoang Duong
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Li Jade
Galej Wojciech P
Oshikane Hiroyuki
Newman Andrew J
Nagai Kiyoshi
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
1878-4186
DOI
10.1016/j.str.2013.04.017
Published
2013-06-04
Pages
910-19
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC3677097
Subset
IM
Grants
Medical Research Council · MC_U105184330 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.str.2013.04.017 PMC Full Text View journal details
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