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  Novel regulatory principles of the spliceosomal Brr2 RNA helicase and links to retinal disease in humans.

Mozaffari-Jovin, S., Wandersleben, T., Santos, K. F., Will, C. L., Lührmann, R., & Wahl, M. C. (2014). Novel regulatory principles of the spliceosomal Brr2 RNA helicase and links to retinal disease in humans. RNA Biology, 11(4), 298-312. doi:10.4161/rna.28353.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-BE00-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-822E-5
Genre: Journal Article

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Mozaffari-Jovin, S.1, Author              
Wandersleben, T., Author
Santos, K. F., Author
Will, C. L.1, Author              
Lührmann, R.1, Author              
Wahl, M. C., Author
Affiliations:
1Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              

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Free keywords: Pre-mRNA splicing; RNA helicase; RNA-protein complex; spliceosome catalytic activation; retinitis pigmentosa
 Abstract: For each round of pre-mRNA splicing, a spliceosome is assembled anew on its substrate. RNA-protein remodeling events required for spliceosome assembly, splicing catalysis, and spliceosome disassembly are driven and controlled by a conserved group of ATPases/RNA helicases. The activities of most of these enzymes are timed by their recruitment to the spliceosome. The Brr2 enzyme, however, which mediates spliceosome catalytic activation, is a stable subunit of the spliceosome, and thus, requires special regulation. Recent structural and functional studies have revealed diverse mechanisms whereby an RNaseH-like and a Jab1/MPN-like domain of the Prp8 protein regulate Brr2 activity during splicing both positively and negatively. Reversible Brr2 inhibition might in part be achieved via an intrinsically unstructured element of the Prp8 Jab1/MPN domain, a concept widespread in biological systems. Mutations leading to changes in the Prp8 Jab1/MPN domain, which are linked to a severe form of retinitis pigmentosa, disrupt Jab1/MPN-mediated regulation of Brr2.

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Language(s): eng - English
 Dates: 2014-03-052014-04
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.4161/rna.28353
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Title: RNA Biology
Source Genre: Journal
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Pages: - Volume / Issue: 11 (4) Sequence Number: - Start / End Page: 298 - 312 Identifier: -