Structural basis for the dual RNA-recognition modes of human Tra2-beta RRM
Human Transformer2-beta (hTra2-beta) is an important member of the serine/arginine-rich protein family, and contains one RNA recognition motif (RRM). It controls the alternative splicing of several pre-mRNAs, including those of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Accordingly, the RRM of hTra2-beta specifically binds to two types of RNA sequences [the CAA and (GAA)2 sequences]. We determined the solution structure of the hTra2-beta RRM (spanning residues Asn110–Thr201), which not only has a canonical RRM fold, but also an unusual alignment of the aromatic amino acids on the beta-sheet surface. We then solved the complex structure of the hTra2-beta RRM with the (GAA)2 sequence, and found that the AGAA tetra-nucleotide was specifically recognized through hydrogen-bond formation with several amino acids on the N- and C-terminal extensions, as well as stacking interactions mediated by the unusually aligned aromatic rings on the beta-sheet surface. Further NMR experiments revealed that the hTra2-beta RRM recognizes the CAA sequence when it is integrated in the stem-loop structure. This study indicates that the hTra2-beta RRM recognizes two types of RNA sequences in different RNA binding modes.
|Author:||Kengo Tsuda, Tatsuhiko Someya, Kanako Kuwasako, Mari Takahashi, Fahu He, Satoru Unzai, Makoto Inoue, Takushi Harada, Satoru Watanabe, Takaho Terada, Naohiro Kobayashi, Mikako Shirouzu, Takanori Kigawa, Akiko Tanaka, Sumio Sugano, Peter Güntert, Shigeyuki Yokoyama, Yutaka Muto|
|Date of Publication (online):||12.11.2010|
|Year of first Publication:||2010|
|Publishing Institution:||Univ.-Bibliothek Frankfurt am Main|
|Source:||Nucleic Acids Research (2010) ; doi: 10.1093/nar/gkq854|
|Institutes:||Biochemie und Chemie|
|Frankfurt Institute for Advanced Studies|
|Dewey Decimal Classification:||570 Biowissenschaften; Biologie|
© The Author(s) 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
|Licence (German):||Veröffentlichungsvertrag für Publikationen ohne Print on Demand|