dc.contributor.author
Bortoli, Francesca De
dc.contributor.author
Neumann, Alexander
dc.contributor.author
Kotte, Ana
dc.contributor.author
Timmermann, Bernd
dc.contributor.author
Schüler, Thomas
dc.contributor.author
Wahl, Markus C.
dc.contributor.author
Loll, Bernhard
dc.contributor.author
Heyd, Florian
dc.date.accessioned
2019-07-18T07:22:49Z
dc.date.available
2019-07-18T07:22:49Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/25103
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2858
dc.description.abstract
In the yeast U1 snRNP the Prp39/Prp42 heterodimer is essential for early steps of spliceosome assembly. In metazoans no Prp42 ortholog exists, raising the question how the heterodimer is functionally substituted. Here we present the crystal structure of murine PRPF39, which forms a homodimer. Structure-guided point mutations disrupt dimer formation and inhibit splicing, manifesting the homodimer as functional unit. PRPF39 expression is controlled by NMD-inducing alternative splicing in mice and human, suggesting a role in adapting splicing efficiency to cell type specific requirements. A phylogenetic analysis reveals coevolution of shortened U1 snRNA and the absence of Prp42, which correlates with overall splicing complexity in different fungi. While current models correlate the diversity of spliceosomal proteins with splicing complexity, our study highlights a contrary case. We find that organisms with higher splicing complexity have substituted the Prp39/Prp42 heterodimer with a PRPF39 homodimer.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
metazoan splicing factor PRPF39
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::547 Organische Chemie
dc.title
Increased versatility despite reduced molecular complexity
dc.type
Wissenschaftlicher Artikel
dc.title.subtitle
evolution, structure and function of metazoan splicing factor PRPF39
dcterms.bibliographicCitation.doi
10.1093/nar/gkz243
dcterms.bibliographicCitation.journaltitle
Nucleic Acids Research
dcterms.bibliographicCitation.number
11
dcterms.bibliographicCitation.pagestart
5867
dcterms.bibliographicCitation.pageend
5879
dcterms.bibliographicCitation.volume
47
dcterms.bibliographicCitation.url
https://doi.org/10.1093/nar/gkz243
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
refubium.funding
Deutsche Forschungsgemeinschaft (DFG)
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin und der DFG gefördert.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
0305-1048
dcterms.isPartOf.eissn
1362-4962