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The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence

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Lahr, Roni M. and Mack, Seshat M. and Héroux, Annie and Blagden, Sarah P. and Bousquet-Antonelli, Cécile and Deragon, Jean-Marc and Berman, Andrea J. (2015) The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5′TOP sequence. Nucleic Acids Research, 43 (16). pp. 8077-8088. ISSN 0305-1048

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Abstract

La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5′TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5′ UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5′TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signaling to ribosome biogenesis.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lahr, Roni M.rml140@pitt.edu
Mack, Seshat M.
Héroux, Annie
Blagden, Sarah P.
Bousquet-Antonelli, Cécile
Deragon, Jean-Marc
Berman, Andrea J.ajb190@pitt.edu
Date: 22 July 2015
Date Type: Publication
Journal or Publication Title: Nucleic Acids Research
Volume: 43
Number: 16
Publisher: Oxford University Press
Page Range: pp. 8077-8088
DOI or Unique Handle: 10.1093/nar/gkv748
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: No
ISSN: 0305-1048
Official URL: https://academic.oup.com/nar/article/43/16/8077/10...
Article Type: Research Article
Date Deposited: 13 May 2020 16:42
Last Modified: 13 May 2020 16:42
URI: http://d-scholarship.pitt.edu/id/eprint/38902

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