4MCE: Crystal structure of the Gas5 GRE Mimic

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.
PDB ID: 4MCEDownload
MMDB ID: 123366
PDB Deposition Date: 2013/8/21
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 2.205  Å
Biological Unit for 4MCE: hexameric; determined by author and by software (PISA)
Molecular Components in 4MCE
Label Count Molecule
Nucleotides(2 molecules)
Gas5 Grem FWD
Molecule annotation
Gas5 Grem REV
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

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