4WKR

LaRP7 wrapping up the 3' hairpin of 7SK non-coding RNA (302-332)

Summary for 4WKR

• Entry DOI: 10.2210/pdb4wkr/pdb
• Descriptor: La-related protein 7, 7SK GGHP4 (300-332) (3 entities in total)
• Functional Keywords: rna-binding protein, rna recognition motif, phosphoprotein, protein, nucleus, la motif, rna binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus, nucleoplasm : Q4G0J3
• Total number of polymer chains: 4
• Total formula weight: 67716.63

Authors

Uchikawa, E.,Natchiar, K.S.,Han, X.,Proux, F.,Roblin, P.,Zhang, E.,Durand, A.,Klaholz, B.P.,Dock-Bregeon, A.-C. (deposition date: 2014-10-03, release date: 2015-03-18, Last modification date: 2024-01-10)

Primary citation

Uchikawa, E.,Natchiar, K.S.,Han, X.,Proux, F.,Roblin, P.,Zhang, E.,Durand, A.,Klaholz, B.P.,Dock-Bregeon, A.C.
Structural insight into the mechanism of stabilization of the 7SK small nuclear RNA by LARP7.
Nucleic Acids Res., 43:3373-3388, 2015

PubMed Abstract: The non-coding RNA 7SK is the scaffold for a small nuclear ribonucleoprotein (7SKsnRNP) which regulates the function of the positive transcription elongation factor P-TEFb in the control of RNA polymerase II elongation in metazoans. The La-related protein LARP7 is a component of the 7SKsnRNP required for stability and function of the RNA. To address the function of LARP7 we determined the crystal structure of its La module, which binds a stretch of uridines at the 3'-end of 7SK. The structure shows that the penultimate uridine is tethered by the two domains, the La-motif and the RNA-recognition motif (RRM1), and reveals that the RRM1 is significantly smaller and more exposed than in the La protein. Sequence analysis suggests that this impacts interaction with 7SK. Binding assays, footprinting and small-angle scattering experiments show that a second RRM domain located at the C-terminus binds the apical loop of the 3' hairpin of 7SK, while the N-terminal domains bind at its foot. Our results suggest that LARP7 uses both its N- and C-terminal domains to stabilize 7SK in a closed structure, which forms by joining conserved sequences at the 5'-end with the foot of the 3' hairpin and has thus functional implications.

PubMed: 25753663
DOI: 10.1093/nar/gkv173

Experimental method

X-RAY DIFFRACTION (3.2 Å)