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

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Molecular and Cellular Biology, December 1998, p. 6897-6909, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Christine M. Smith and Joan A. Steitz^*

Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, Connecticut

Received 10 July 1998/Accepted 18 August 1998

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 11introns of the mouse gas5 gene are nine (10 in human) box C/DsnoRNAs predicted to function in the 2'-O-methylation of rRNA.The only regions of conservation between mouse and human gas5genes are their snoRNAs and 5'-end sequences. Mapping the 5' endof the mouse gas5 transcript demonstrates that it possesses anoligopyrimidine tract characteristic of the 5'-terminal oligopyrimidine(5'TOP) class of genes. Arrest of cell growth or inhibition oftranslation by cycloheximide, pactamycin, or rapamycin $---$ which specificallyinhibits the translation of 5'TOP mRNAs $---$ results in accumulationof the gas5 spliced RNA. Classification of gas5 as a 5'TOP geneprovides an explanation for why it is a growth arrest specifictranscript: while the spliced gas5 RNA is normally associatedwith ribosomes and rapidly degraded, during arrested cell growthit accumulates in mRNP particles, as has been reported for other5'TOP messages. Strikingly, inspection of the 5'-end sequencesof currently known snoRNA host gene transcripts reveals that theyall exhibit features of the 5'TOP genefamily.

^* Corresponding author. Mailing address: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute,Yale University, 295 Congress Ave., New Haven, CT 06536. Phone:(203) 737-4417. Fax: (203) 624-8213. E-mail: joan.steitz{at}yale.edu.

Present address: Fred Hutchinson Cancer Research Center, Seattle,Wash.

Molecular and Cellular Biology, December 1998, p. 6897-6909, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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