Fisher: a program for the detection of H/ACA snoRNAs using MFE secondary structure prediction and comparative genomics – assessment and update

BackgroundThe H/ACA family of small nucleolar RNAs (snoRNAs) plays a central role in guiding the pseudouridylation of ribosomal RNA (rRNA). In an effort to systematically identify the complete set of rRNA-modifying H/ACA snoRNAs from the genome sequence of the budding yeast, Saccharomyces cerevisiae, we developed a program – Fisher – and previously presented several candidate snoRNAs based on our analysis [1].FindingsIn this report, we provide a brief update of this work, which was aborted after the publication of experimentally-identified snoRNAs [2] identical to candidates we had identified bioinformatically using Fisher. Our motivation for revisiting this work is to report on the status of the candidate snoRNAs described in [1], and secondly, to report that a modified version of Fisher together with the available multiple yeast genome sequences was able to correctly identify several H/ACA snoRNAs for modification sites not identified by the snoGPS program [3]. While we are no longer developing Fisher, we briefly consider the merits of the Fisher algorithm relative to snoGPS, which may be of use for workers considering pursuing a similar search strategy for the identification of small RNAs. The modified source code for Fisher is made available as supplementary material.ConclusionOur results confirm the validity of using minimum free energy (MFE) secondary structure prediction to guide comparative genomic screening for RNA families with few sequence constraints.

[1]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[2]  Tamás Kiss,et al.  Site-Specific Pseudouridine Formation in Preribosomal RNA Is Guided by Small Nucleolar RNAs , 1997, Cell.

[3]  S. Stamm,et al.  The snoRNA HBII-52 Regulates Alternative Splicing of the Serotonin Receptor 2C , 2006, Science.

[4]  P. Wincker,et al.  Genomic Exploration of the Hemiascomycetous Yeasts: 6. Saccharomyces exiguus , 2000, FEBS letters.

[5]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[6]  B. Birren,et al.  Sequencing and comparison of yeast species to identify genes and regulatory elements , 2003, Nature.

[7]  Walter Fontana,et al.  Fast folding and comparison of RNA secondary structures , 1994 .

[8]  B. Dujon,et al.  Genome evolution in yeasts , 2004, Nature.

[9]  Wayne A. Decatur,et al.  Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome. , 2004, Nucleic acids research.

[10]  George Newport,et al.  The diploid genome sequence of Candida albicans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  L. Fulton,et al.  Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting , 2003, Science.

[12]  S. Eddy,et al.  Computational identification of non-coding RNAs in Saccharomyces cerevisiae by comparative genomics. , 2003, Nucleic acids research.

[13]  J. Bachellerie,et al.  Intron-encoded, antisense small nucleolar RNAs: the characterization of nine novel species points to their direct role as guides for the 2'-O-ribose methylation of rRNAs. , 1996, Journal of molecular biology.

[14]  S. Eddy,et al.  Homologs of small nucleolar RNAs in Archaea. , 2000, Science.

[15]  Kara Dolinski,et al.  Saccharomyces Genome Database (SGD) provides biochemical and structural information for budding yeast proteins , 2003, Nucleic Acids Res..

[16]  J. Bachellerie,et al.  Archaeal homologs of eukaryotic methylation guide small nucleolar RNAs: lessons from the Pyrococcus genomes. , 2000, Journal of molecular biology.

[17]  Vincent Moulton,et al.  A Search for H/ACA SnoRNAs in Yeast Using MFE Secondary Structure Prediction , 2003, Bioinform..

[18]  J. Ni,et al.  Small Nucleolar RNAs Direct Site-Specific Synthesis of Pseudouridine in Ribosomal RNA , 1997, Cell.

[19]  I. Behm-Ansmant,et al.  Combined in silico and experimental identification of the Pyrococcus abyssi H/ACA sRNAs and their target sites in ribosomal RNAs , 2008, Nucleic acids research.

[20]  Liang-Hu Qu,et al.  snoSeeker: an advanced computational package for screening of guide and orphan snoRNA genes in the human genome , 2006, Nucleic acids research.

[21]  B. Barrell,et al.  The genome sequence of Schizosaccharomyces pombe , 2002, Nature.

[22]  S. Eddy,et al.  A computational screen for methylation guide snoRNAs in yeast. , 1999, Science.

[23]  Peter F. Stadler,et al.  SnoReport: computational identification of snoRNAs with unknown targets , 2008, Bioinform..

[24]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[25]  Tamás Kiss,et al.  Site-Specific Ribose Methylation of Preribosomal RNA: A Novel Function for Small Nucleolar RNAs , 1996, Cell.

[26]  P. Philippsen,et al.  The Ashbya gossypii Genome as a Tool for Mapping the Ancient Saccharomyces cerevisiae Genome , 2004, Science.

[27]  A. Hüttenhofer,et al.  The expanding snoRNA world. , 2002, Biochimie.

[28]  Gwenael Badis,et al.  The complete set of H/ACA snoRNAs that guide rRNA pseudouridylations in Saccharomyces cerevisiae. , 2005, RNA.