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Title: Structure of the central RNA recognition motif of human TIA-1 at 1.95 A resolution

Abstract

T-cell-restricted intracellular antigen-1 (TIA-1) regulates alternative pre-mRNA splicing in the nucleus, and mRNA translation in the cytoplasm, by recognizing uridine-rich sequences of RNAs. As a step towards understanding RNA recognition by this regulatory factor, the X-ray structure of the central RNA recognition motif (RRM2) of human TIA-1 is presented at 1.95 A resolution. Comparison with structurally homologous RRM-RNA complexes identifies residues at the RNA interfaces that are conserved in TIA-1-RRM2. The versatile capability of RNP motifs to interact with either proteins or RNA is reinforced by symmetry-related protein-protein interactions mediated by the RNP motifs of TIA-1-RRM2. Importantly, the TIA-1-RRM2 structure reveals the locations of mutations responsible for inhibiting nuclear import. In contrast with previous assumptions, the mutated residues are buried within the hydrophobic interior of the domain, where they would be likely to destabilize the RRM fold rather than directly inhibit RNA binding.

Authors:
 [1];  [2];  [3]
  1. Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States)
  2. Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205 (United States)
  3. Bruker AXS Inc., 5465 East Cheryl Parkway, Madison, WI 53711 (United States)
Publication Date:
OSTI Identifier:
21043666
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 367; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2008.01.027; PII: S0006-291X(08)00048-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CYTOPLASM; MUTATIONS; PROTEINS; RNA; SPATIAL RESOLUTION; SPLICING; URIDINE; X RADIATION

Citation Formats

Kumar, Amit O, Swenson, Matthew C, Benning, Matthew M, and Kielkopf, Clara L. Structure of the central RNA recognition motif of human TIA-1 at 1.95 A resolution. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.01.027.
Kumar, Amit O, Swenson, Matthew C, Benning, Matthew M, & Kielkopf, Clara L. Structure of the central RNA recognition motif of human TIA-1 at 1.95 A resolution. United States. https://doi.org/10.1016/j.bbrc.2008.01.027
Kumar, Amit O, Swenson, Matthew C, Benning, Matthew M, and Kielkopf, Clara L. 2008. "Structure of the central RNA recognition motif of human TIA-1 at 1.95 A resolution". United States. https://doi.org/10.1016/j.bbrc.2008.01.027.
@article{osti_21043666,
title = {Structure of the central RNA recognition motif of human TIA-1 at 1.95 A resolution},
author = {Kumar, Amit O and Swenson, Matthew C and Benning, Matthew M and Kielkopf, Clara L.},
abstractNote = {T-cell-restricted intracellular antigen-1 (TIA-1) regulates alternative pre-mRNA splicing in the nucleus, and mRNA translation in the cytoplasm, by recognizing uridine-rich sequences of RNAs. As a step towards understanding RNA recognition by this regulatory factor, the X-ray structure of the central RNA recognition motif (RRM2) of human TIA-1 is presented at 1.95 A resolution. Comparison with structurally homologous RRM-RNA complexes identifies residues at the RNA interfaces that are conserved in TIA-1-RRM2. The versatile capability of RNP motifs to interact with either proteins or RNA is reinforced by symmetry-related protein-protein interactions mediated by the RNP motifs of TIA-1-RRM2. Importantly, the TIA-1-RRM2 structure reveals the locations of mutations responsible for inhibiting nuclear import. In contrast with previous assumptions, the mutated residues are buried within the hydrophobic interior of the domain, where they would be likely to destabilize the RRM fold rather than directly inhibit RNA binding.},
doi = {10.1016/j.bbrc.2008.01.027},
url = {https://www.osti.gov/biblio/21043666}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 367,
place = {United States},
year = {Fri Mar 21 00:00:00 EDT 2008},
month = {Fri Mar 21 00:00:00 EDT 2008}
}