5knw
From Proteopedia
Solution NMR structure of human LARP7 xRRM2
Structural highlights
Disease[LARP7_HUMAN] Microcephalic primordial dwarfism, Alazami type. The disease is caused by mutations affecting the gene represented in this entry. Function[LARP7_HUMAN] Negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system. Within the 7SK RNP complex, the positive transcription elongation factor b (P-TEFb) is sequestered in an inactive form, preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation.[1] [2] Publication Abstract from PubMedThe 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 La module 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 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. hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA.,Eichhorn CD, Chug R, Feigon J Nucleic Acids Res. 2016 Sep 26. pii: gkw833. PMID:27679474[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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