TY - JOUR A1 - Tsuda, Kengo A1 - Kuwasako, Kanako A1 - Takahashi, Mari A1 - Someya, Tatsuhiko A1 - Inoue, Makoto A1 - Terada, Takaho A1 - Kobayashi, Naohiro A1 - Shirouzu, Mikako A1 - Kigawa, Takanori A1 - Tanaka, Akiko A1 - Sugano, Sumio A1 - Güntert, Peter A1 - Muto, Yutaka A1 - Yokoyama, Shigeyuki T1 - Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3 T2 - Nucleic acids research N2 - 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. Y1 - 2009 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6707 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-68081 SN - 1362-4962 SN - 0305-1048 N1 - © 2009 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. VL - 37 IS - 15 SP - 5151 EP - 5166 PB - Oxford Univ. Press CY - Oxford ER -