Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3

  • The CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-like factors (CELF) family or the Bruno-like family and is involved in the control of splicing, translation and mRNA degradation. Several target RNA sequences of CUG-BP1 have been predicted, such as the CUG triplet repeat, the GU-rich sequences and the AU-rich element of nuclear pre-mRNAs and/or cytoplasmic mRNA. CUG-BP1 has three RNA-recognition motifs (RRMs), among which the third RRM (RRM3) can bind to the target RNAs on its own. In this study, we solved the solution structure of the CUG-BP1 RRM3 by hetero-nuclear NMR spectroscopy. The CUG-BP1 RRM3 exhibited a noncanonical RRM fold, with the four-stranded b-sheet surface tightly associated with the N-terminal extension. Furthermore, we determined the solution structure of the CUG-BP1 RRM3 in the complex with (UG)3 RNA, and discovered that the UGU trinucleotide is specifically recognized through extensive stacking interactions and hydrogen bonds within the pocket formed by the b-sheet surface and the N-terminal extension. This study revealed the unique mechanism that enables the CUG-BP1 RRM3 to discriminate the short RNA segment from other sequences, thus providing the molecular basis for the comprehension of the role of the RRM3s in the CELF/Bruno-like family.
Author:Kengo Tsuda, Kanako KuwasakoORCiD, Mari Takahashi, Tatsuhiko Someya, Makoto Inoue, Takaho Terada, Naohiro Kobayashi, Mikako Shirouzu, Takanori Kigawa, Akiko Tanaka, Sumio Sugano, Peter GüntertORCiDGND, Yutaka Muto, Shigeyuki Yokoyama
Pubmed Id:
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Date of Publication (online):2009/08/10
Date of first Publication:2009/06/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/08/10
Page Number:16
First Page:5151
Last Page:5166
© 2009 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source:Nucleic Acids Research, 2009, 1–16 ; doi:10.1093/nar/gkp546
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 2.0