Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR

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Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR

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Title: Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR
Author: Durney, Michael Anthony; D'Souza, Victoria M.

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Citation: Durney, Michael Anthony, and Victoria M. D'Souza. 2010. Preformed protein-binding motifs in 7SK snRNA: Structural and thermodynamic comparisons with retroviral TAR. Journal of Molecular Biology 404(4): 555–567.
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Abstract: The 7SK small nuclear RNA is a highly conserved non-coding RNA that regulates transcriptional elongation. 7SK utilizes the HEXIM proteins to sequester the transcription factor P-TEFb by a mechanism similar to that used by retroviral TAR RNA to engage Tat and P-TEFb. Tat has also recently been shown to bind 7SK directly and recruit P-TEFb to TAR. We report here the solution structures of the free and arginine-bound forms of stem loop 4 of 7SK (7SK-SL4). Comparison of the 7SK-SL4 and TAR structures demonstrates the presence of a common arginine sandwich motif. However, arginine binding to 7SK-SL4 is mechanistically distinct and occurs via docking into a pre-organized pocket resulting in a 1000-fold increased affinity. Furthermore, whereas formation of the binding pocket in TAR requires a critical base-triple, hydrogen-bond formation between the equivalent bases in 7SK-SL4 is not essential and the pocket is stabilized solely by a pseudo base-triple platform. In addition, this theme of preformed protein binding motifs also extends into the pentaloop. The configuration of the loop suggests that 7SK-SL4 is poised to make ternary contacts with P-TEFb and HEXIM or Tat. These key differences between 7SK-SL4 and TAR present an opportunity to understand RNA structural adaptation and have implications for understanding differential interactions with Tat.
Published Version: doi:10.1016/j.jmb.2010.08.042
Other Sources: http://www.ncbi.nlm.nih.gov/pubmed/20816986
Terms of Use: This article is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#OAP
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:9282599

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  • FAS Scholarly Articles [6464]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University
 
 

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