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Title: hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA

The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal Lamodule binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear.We report the solution NMR structure of the hLARP7 CTD and show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3' end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study thus confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function.
Authors:
 [1] ;  [1] ;  [1]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry
Publication Date:
Grant/Contract Number:
FC03-02ER63421; GM107567; T32 CA009056; 14POST20380737; 126777-PF-14-179- 01-DMC
Type:
Accepted Manuscript
Journal Name:
Nucleic Acids Research
Additional Journal Information:
Journal Volume: 44; Journal Issue: 20; Journal ID: ISSN 0305-1048
Publisher:
Oxford University Press
Research Org:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23). Biological Systems Science Division; National Inst. for Health (NIH); American Heart Association (AHA); American Cancer Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE
OSTI Identifier:
1427800