Structural and functional analysis of RNA and TAP binding to SF2/ASF.
The serine/arginine-rich (SR) protein splicing factor 2/alternative splicing factor (SF2/ASF) has a role in splicing, stability, export and translation of messenger RNA. Here, we present the structure of the RNA recognition motif (RRM) 2 from SF2/ASF, which has an RRM fold with a considerably extended loop 5 region, containing a two-stranded beta-sheet. The loop 5 extension places the previously identified SR protein kinase 1 docking sequence largely within the RRM fold. We show that RRM2 binds to RNA in a new way, by using a tryptophan within a conserved SWQLKD motif that resides on helix alpha1, together with amino acids from strand beta2 and a histidine on loop 5. The linker connecting RRM1 and RRM2 contains arginine residues, which provide a binding site for the mRNA export factor TAP, and when TAP binds to this region it displaces RNA bound to RRM2.
Tintaru
Aura M
AM
Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
Hautbergue
Guillaume M
GM
Hounslow
Andrea M
AM
Hung
Ming-Lung
ML
Lian
Lu-Yun
LY
Craven
C Jeremy
CJ
Wilson
Stuart A
SA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D017433:Protein Structure, Secondary; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry*; D000068103:Serine-Arginine Splicing Factors; D014364:Tryptophan / Q000737:chemistry / Q000235:genetics
C122111:NXF1 protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D014364:Tryptophan; D001120:Arginine; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases