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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′ te...

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Autores principales: Eichhorn, Catherine D., Chug, Rahul, Feigon, Juli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175362/
https://www.ncbi.nlm.nih.gov/pubmed/27679474
http://dx.doi.org/10.1093/nar/gkw833
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author Eichhorn, Catherine D.
Chug, Rahul
Feigon, Juli
author_facet Eichhorn, Catherine D.
Chug, Rahul
Feigon, Juli
author_sort Eichhorn, Catherine D.
collection PubMed
description 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 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.
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spelling pubmed-51753622016-12-27 hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA Eichhorn, Catherine D. Chug, Rahul Feigon, Juli Nucleic Acids Res Structural Biology 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 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. Oxford University Press 2016-11-16 2016-09-26 /pmc/articles/PMC5175362/ /pubmed/27679474 http://dx.doi.org/10.1093/nar/gkw833 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Structural Biology
Eichhorn, Catherine D.
Chug, Rahul
Feigon, Juli
hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA
title hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA
title_full hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA
title_fullStr hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA
title_full_unstemmed hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA
title_short hLARP7 C-terminal domain contains an xRRM that binds the 3′ hairpin of 7SK RNA
title_sort hlarp7 c-terminal domain contains an xrrm that binds the 3′ hairpin of 7sk rna
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175362/
https://www.ncbi.nlm.nih.gov/pubmed/27679474
http://dx.doi.org/10.1093/nar/gkw833
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