Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and 9G8.
The sequence-specific RNA-binding proteins SRp20 and 9G8 are the smallest members of the serine- and arginine-rich (SR) protein family, well known for their role in splicing. They also play a role in mRNA export, in particular of histone mRNAs. We present the solution structures of the free 9G8 and SRp20 RNA recognition motifs (RRMs) and of SRp20 RRM in complex with the RNA sequence 5'CAUC3'. The SRp20-RNA structure reveals that although all 4 nt are contacted by the RRM, only the 5' cytosine is primarily recognized in a specific way. This might explain the numerous consensus sequences found by SELEX (systematic evolution of ligands by exponential enrichment) for the RRM of 9G8 and SRp20. Furthermore, we identify a short arginine-rich peptide adjacent to the SRp20 and 9G8 RRMs, which does not contact RNA but is necessary and sufficient for interaction with the export factor Tip-associated protein (TAP). Together, these results provide a molecular description for mRNA and TAP recognition by SRp20 and 9G8.
Hargous
Yann
Y
Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
Hautbergue
Guillaume M
GM
Tintaru
Aura M
AM
Skrisovska
Lenka
L
Golovanov
Alexander P
AP
Stevenin
James
J
Lian
Lu-Yun
LY
Wilson
Stuart A
SA
Allain
Frédéric H-T
FH
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020816:Amino Acid Motifs; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors
D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D010455:Peptides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors