2M8D

Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'

Summary for 2M8D

• Entry DOI: 10.2210/pdb2m8d/pdb
• NMR Information: BMRB: 19248
• Descriptor: RNA (5'-R(*UP*GP*AP*AP*GP*GP*AP*C)-3'), Serine/arginine-rich splicing factor 1 (2 entities in total)
• Functional Keywords: sr protein, pseudo-rrm, rrm, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q07955
• Total number of polymer chains: 2
• Total formula weight: 12928.23

Authors

Clery, A.,Sinha, R.,Anczukow, O.,Corrionero, A.,Moursy, A.,Daubner, G.,Valcarcel, J.,Krainer, A.R.,Allain, F.H.T. (deposition date: 2013-05-17, release date: 2013-07-10, Last modification date: 2024-05-15)

Primary citation

Clery, A.,Sinha, R.,Anczukow, O.,Corrionero, A.,Moursy, A.,Daubner, G.M.,Valcarcel, J.,Krainer, A.R.,Allain, F.H.
Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition.
Proc.Natl.Acad.Sci.USA, 110:E2802-E2811, 2013

PubMed Abstract: Serine/arginine (SR) proteins, one of the major families of alternative-splicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one α-helix and does not involve the β-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo-RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound α-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM.

PubMed: 23836656
DOI: 10.1073/pnas.1303445110

Experimental method

SOLUTION NMR