1. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2. Genomic Sciences Center and Cellular Signaling Laboratory, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0106, Japan
3. Department of Biology, Faculty of Science, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-0013, Japan
4. Department of Biophysics, Faculty of Science, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8224, Japan
5. Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan

Correspondence to: Shigeyuki Yokoyama^1,2 Correspondence and requests for materials should be addressed to S.Y.
(e-mail: Email: yokoyama@y-sun.biochem.s.u-tokyo.ac.jp).The coordinates for the Sxl RNA complex have been deposited in the Brook haven Protein Data Bank, accession code 1B7F.

Abstract

The Sex-lethal (Sxl) protein of Drosophila melanogaster regulates alternative splicing of the transformer (tra) messenger RNA precursor by binding to the tra polypyrimidine tract during the sex-determination process. The crystal structure has now been determined at 2.6 Å resolution of the complex formed between two tandemly arranged RNA-binding domains of the Sxl protein and a 12-nucleotide, single-stranded RNA derived from the tra polypyrimidine tract. The two RNA-binding domains have their -sheet platforms facing each other to form a V-shaped cleft. The RNA is characteristically extended and bound in this cleft, where the UGUUUUUUU sequence is specifically recognized by the protein. This structure offers the first insight, to our knowledge, into how a protein binds specifically to a cognate RNA without any intramolecular base-pairing.