SRA and its binding partners: an expanding role for RNA-binding coregulators in nuclear receptor-mediated gene regulation

Abstract

The discovery that SRA RNA can function as a nuclear receptor (NR) coactivator resulted in a fundamental change in the perception of how NRs and their coregulators may regulate hormone signaling pathways. The subsequent identification of molecules capable of binding SRA, including SHARP, p68, and more recently SLIRP, which also function as coregulators, has further broadened our understanding of NR-dependent gene regulation. The integral role that NRs play in directing developmental, metabolic and pathological programs of transcription has defined them as paramount targets for treating a broad range of human diseases. Thus with a greater understanding of SRA and its interactions with its binding partners, novel RNA–protein interactions may be identified and exploited for therapeutic gain. Here we discuss the isolation of SRA, its impact on NR activity and interactions with known binding partners.

Keywords::

• SRA
• RNA-binding proteins
• SLIRP
• coregulators
• nuclear receptor

Acknowledgments

The authors are grateful to Kavitha Iyer for her critical review and input into this manuscript, and to the various funding organizations that have contributed, including the National Health and Medical Research Council, National Breast Cancer Foundation, Cancer Council of WA, the Royal Perth Hospital Medical Research Foundation and the Centre for Food and Genomic Medicine.

Declaration of interest: The authors report no conflicts of interest.

Editor: Marvin Wickens