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
| Title: | Preformed Protein-Binding Motifs in 7SK snRNA: Structural and Thermodynamic Comparisons with Retroviral TAR |
| Author: |
Durney, Michael Anthony; D'Souza, Victoria M.
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
preformed_protein_binding.pdf (218.5Kb; PDF) 
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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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