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Nucleic Acids Research 2004 32(14):4281-4296; doi:10.1093/nar/gkh768
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Published online 11 August 2004

Nucleic Acids Research, Vol. 32 No. 14 © Oxford University Press 2004; all rights reserved

Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome

Peter Schattner1,3, Wayne A. Decatur4, Carrie A. Davis2,3, Manuel Ares, Jr2,3, Maurille J. Fournier4 and Todd M. Lowe1,3,*

1 Department of Biomolecular Engineering, 2 Department of Molecular, Cell, and Developmental Biology and 3 UCSC RNA Center, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA and 4 Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA

* To whom correspondence should be addressed. Tel: +1 831 459 1511; Fax: +1 831 459 3139; Email: lowe{at}cse.ucsc.edu
Correspondence may also be addressed to Peter Schattner. Email: schattner{at}cse.ucsc.edu

Received June 15, 2004; Revised July 15, 2004; Accepted July 26, 2004

One of the largest families of small RNAs in eukaryotes is the H/ACA small nucleolar RNAs (snoRNAs), most of which guide RNA pseudouridine formation. So far, an effective computational method specifically for identifying H/ACA snoRNA gene sequences has not been established. We have developed snoGPS, a program for computationally screening genomic sequences for H/ACA guide snoRNAs. The program implements a deterministic screening algorithm combined with a probabilistic model to score gene candidates. We report here the results of testing snoGPS on the budding yeast Saccharomyces cerevisiae. Six candidate snoRNAs were verified as novel RNA transcripts, and five of these were verified as guides for pseudouridine formation at specific sites in ribosomal RNA. We also predicted 14 new base-pairings between snoRNAs and known pseudouridine sites in S.cerevisiae rRNA, 12 of which were verified by gene disruption and loss of the cognate pseudouridine site. Our findings include the first prediction and verification of snoRNAs that guide pseudouridine modification at more than two sites. With this work, 41 of the 44 known pseudouridine modifications in S.cerevisiae rRNA have been linked with a verified snoRNA, providing the most complete accounting of the H/ACA snoRNAs that guide pseudouridylation in any species.


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