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Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein

Nature volume 398, pages 579–585 (1999)Cite this article

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 β-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.

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Figure 1: Sequence and secondary-structure alignment of the RBD(s) of Sxl, U1A and hnRNP A1 (8–10).
Figure 2: The structure of the complex between the Sxl protein (RBD1–RBD2) and the 12-nucleotide RNA derived from the tra polypyrimidine tract (stereo view).
Figure 3: Distribution of the electrostatic potential on the solvent-accessible surface of Sxl (stereo view).
Figure 4: The U3–U11 (UGUUUUUUU) RNA segment in the complex (stereo view).
Figure 5: Recognition of U3–U11 (UGUUUUUUU) by the Sxl RBD1 and RBD2 domains.
Figure 6: Protein–RNA interactions of the Sxl and U1A RBDs.

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Acknowledgements

We thank D. G. Vassylyev for helpful discussions, and M. Horikoshi for data collection. This work was supported in part by Grants-in-Aid for Scientific Research on Priority Areas to S.Y. from the Ministry of Education, Science, Culture and Sports of Japan.

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Authors and Affiliations

  1. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Noriko Handa, Osamu Nureki, Kazuki Kurimoto, Insil Kim, Yutaka Muto & Shigeyuki Yokoyama

  2. Genomic Sciences Center and Cellular Signaling Laboratory, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, 351-0106, Saitama, Japan

    Osamu Nureki & Shigeyuki Yokoyama

  3. Department of Biology, Faculty of Science, Kobe University, 1-1 Rokkodaicho, Nada-ku, 657-0013, Kobe, Japan

    Hiroshi Sakamoto

  4. Department of Biophysics, Faculty of Science, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, 606-8224, Kyoto, Japan

    Yoshiro Shimura

  5. Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, 565-0874, Osaka, Japan

    Yoshiro Shimura

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Correspondence to Shigeyuki Yokoyama.

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Handa, N., Nureki, O., Kurimoto, K. et al. Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein. Nature 398, 579–585 (1999). https://doi.org/10.1038/19242

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