The fact that in humans, most snoRNAs are encoded in the introns of proteincoding and non-protein-coding genes gave rise to the assumption that these host genes act solely as cellular housekeepers via their snoRNA-encoding sequences. However, recent studies have challenged this concept and have implicated snoRNAs and their host genes in the control of oncogenesis and cell fate. The existence of a number of ��orphan�� snoRNAs with no known rRNA targets, and the demonstration of their presence in subcellular locations other than the nucleolus, supports the concept that this group of small non-coding RNAs may regulate other molecules and have additional cellular functions. Furthermore, a number of studies suggest an evolutionary relationship between miRNAs and snoRNAs and others report that mature snoRNAs may undergo further cellular processing to form smaller snoRNA-derived RNAs with miRNA-like functions. Additionally, snoRNA expression has been shown to be as variable as miRNA expression in human Thapsigargin tumour samples and normalising miRNA polymerase chain reaction expression data to these snoRNAs introduced bias in associations between miRNA and outcome. The growth arrest-specific transcript 5 gene, located at 1q25, is a non-protein-coding multiple snoRNA host gene comprising of 12 exons initially discovered during screening for potential tumor suppressor genes expressed at high levels during growth arrest. In humans, it encodes ten intronic C/D box snoRNAs and two mature long non-coding RNAs isoforms that originate from alternative 59-splice donor sites in exon 7. The open reading frame encoded within GAS5 exons is short and is not thought to encode a functional protein. Mapping of its 5* end demonstrates that it possesses an oligopyrimidine tract characteristic of the 5*-terminal oligopyrimidine class of genes that accumulate during cell cycle arrest but are RU 58668 rapidly degraded by nonsense-mediated decay during cell growth. The classification of GAS5 as a 5*TOP gene offers an explanation as to why it is a growth arrest specific transcript as while the spliced GAS5 RNA is normally associated with ribosomes and rapidly degraded, during arrested cell growth it accumulates in mRNP particles. Interestingly, the only regions of conservation between mouse and human GAS5 genes are their snoRNAs and 5*-end sequences suggesting that these are the most important functional components.