Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate

Journal Article · Tue Dec 23 00:00:00 EST 2014 · Nat. Commun.

DOI:https://doi.org/10.1038/ncomms6395· OSTI ID:1163790

Hudson, William H.; Pickard, Mark R.; Kuiper, Emily G.; Mourtada-Maarabouni, Mirna; Conn, Graeme L.; Kojetin, Douglas J.; Williams, Gwyn T.; Ortlund, Eric A. ^[1]

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1. Emory-MED

The majority of the eukaryotic genome is transcribed, generating a significant number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent the most poorly understood product of transcription, recent work has shown lincRNAs fulfill important cellular functions. In addition to low sequence conservation, poor understanding of structural mechanisms driving lincRNA biology hinders systematic prediction of their function. Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. We identify the functional Gas5-SR interface and generate point mutations that ablate the SR-Gas5 lincRNA interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we find that the Gas5 SR-recognition sequence is conserved among haplorhines, with its evolutionary origin as a splice acceptor site. This study demonstrates that lincRNAs can recognize protein targets in a conserved, sequence-specific manner in order to affect critical cell functions.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: UNIVERSITYOTHER
• OSTI ID: 1163790
• Journal Information: Nat. Commun., Vol. 5, Issue 11, 2014
• Country of Publication: United States
• Language: ENGLISH