Nature communications, 2014-11, Vol.5 (1), p.5395-5395, Article 5395
2014
Details
- Autor(en) / Beteiligte
- Titel
- Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate
- Ist Teil von
- Nature communications, 2014-11, Vol.5 (1), p.5395-5395, Article 5395
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/ncomms6395Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4280027
- Format
- –
- Schlagworte
- Amino Acid Sequence, Apoptosis, Apoptosis - genetics, Apoptosis - physiology, Base Sequence, Breast Neoplasms - pathology, Cell cycle, Cell Line, Tumor, Cell Proliferation - genetics, Cell Proliferation - physiology, Conserved Sequence, Female, Genes, Genomes, Humans, Magnetic Resonance Spectroscopy, Male, Models, Genetic, Mutation - genetics, Prostatic Neoplasms - pathology, Proteins, Receptors, Steroid - genetics, Receptors, Steroid - physiology, Response Elements - genetics, Response Elements - physiology, RNA, Long Noncoding - chemistry, RNA, Long Noncoding - genetics, RNA, Long Noncoding - physiology, RNA, Small Nucleolar - chemistry, RNA, Small Nucleolar - genetics, RNA, Small Nucleolar - physiology, Steroids, Transcription, Genetic - genetics, Transcription, Genetic - physiology