Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes

We have identified gas5 (growth arrest-specific transcript 5) as a non-protein-coding multiple small nucleolar RNA (snoRNA) host gene similar to UHG (U22 host gene). Encoded within the 11 introns of the mouse gad gene are nine (10 in human) box CID snoRNAs predicted to function in the 2'-O-methylation of rRNA. The only regions of conservation between mouse and human gad genes are their snoRNAs and 5'-end sequences. Mapping the 5' end of the mouse gas5 transcript demonstrates that it possesses an oligopyrimidine tract characteristic of the 5'-terminal oligopyrimidine (5'TOP) class of genes. Arrest of cell growth or inhibition of translation by cycloheximide, pactamycin, or rapamycin-which specifically inhibits the translation of 5'TOP mRNAs-results in accumulation of the gad spliced RNA. Classification of gas5 as a 5'TOP gene provides an explanation for why it is a growth arrest specific transcript: while the spliced gas5 RNA is normally associated with ribosomes and rapidly degraded, during arrested cell growth it accumulates in mRNP particles, as has been reported for other 5'TOP messages. Strikingly, inspection of the 5' end sequences of currently known snoRNA host gene transcripts reveals that they all exhibit features of the 5'TOP gene family.