GAS5 Gene

Abstract

Growth arrest‐specific 5 ( GAS5 ) is a nonprotein‐coding small nucleolar ribonucleic acid (snoRNA) host gene. Ten box C/D snoRNAs are encoded within the 11 introns of the human GAS5 gene, whereas the spliced exons have little protein‐coding potential. GAS5 has been classified as a member of the 5′ oligopyrimidine tract (5′ TOP) gene family. Growth‐dependent translation mediated by the 5′ TOP sequence determines the level of the GAS5 spliced transcript ( GAS5 long noncoding RNA (lncRNA)) by a mechanism of translation‐linked RNA degradation. GAS5 lncRNA plays a critical role in arresting cell growth and inducing apoptosis. The decreased expression of GAS5 in multiple cancers suggests that GAS5 acts as a tumour suppressor. GAS5 lncRNA controls the gene expression of critical cell cycle and apoptosis regulators. GAS5 lncRNA suppresses steroid‐responsive transcription by direct association with several steroid receptors and acts as a molecular decoy. GAS5 lncRNA also sequestrates a specific functional microRNA. Key Concepts GAS5 is a nonprotein‐coding small nucleolar RNA host gene. A translation‐linked mRNA decay pathway controls growth arrest‐specific accumulation of GAS5 by way of its 5′‐terminal oligopyrimidine tract (5′ TOP). GAS5 functions to arrest cell growth and induce apoptosis. GAS5 controls expression of genes for critical regulators of the cell cycle and apoptosis. GAS5 binds to steroid hormone receptors through its 3′‐terminal stem‐loop structure to suppress steroid‐responsive transcription. GAS5 sequestrates a specific functional microRNA.