Computer identification of snoRNA genes using a Mammalian Orthologous Intron Database

Based on comparative genomics, we created a bioinformatic package for computer prediction of small nucleolar RNA (snoRNA) genes in mammalian introns. The core of our approach was the use of the Mammalian Orthologous Intron Database (MOID), which contains all known introns within the human, mouse and rat genomes. Introns from orthologous genes from these three species, that have the same position relative to the reading frame, are grouped in a special orthologous intron table. Our program SNO.pl searches for conserved snoRNA motifs within MOID and reports all cases when characteristic snoRNA-like structures are present in all three orthologous introns of human, mouse and rat sequences. Here we report an example of the SNO.pl usage for searching a particular pattern of conserved C/D-box snoRNA motifs (canonical C- and D-boxes and the 6 nt long terminal stem). In this computer analysis, we detected 57 triplets of snoRNA-like structures in three mammals. Among them were 15 triplets that represented known C/D-box snoRNA genes. Six triplets represented snoRNA genes that had only been partially characterized in the mouse genome. One case represented a novel snoRNA gene, and another three cases, putative snoRNAs. Our programs are publicly available and can be easily adapted and/or modified for searching any conserved motifs within mammalian introns.

[1]  B. Cullen Transcription and processing of human microRNA precursors. , 2004, Molecular cell.

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

[3]  Alexei Fedorov,et al.  Large-scale comparison of intron positions among animal, plant, and fungal genes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Tollervey,et al.  Insights into the structure and function of a guide RNP , 2003, Nature Structural Biology.

[5]  Iraj Daizadeh,et al.  EID: the Exon?Intron Database?an exhaustive database of protein-coding intron-containing genes , 2000, Nucleic Acids Res..

[6]  Alexei Fedorov,et al.  Mystery of intron gain. , 2003, Genome research.

[7]  Alexander Hüttenhofer,et al.  Experimental RNomics: a global approach to identifying small nuclear RNAs and their targets in different model organisms. , 2004, Methods in molecular biology.

[8]  A. Hüttenhofer,et al.  RNomics: an experimental approach that identifies 201 candidates for novel, small, non‐messenger RNAs in mouse , 2001, The EMBO journal.

[9]  W. Gilbert,et al.  Large-scale comparison of intron positions in mammalian genes shows intron loss but no gain , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Alexei Fedorov,et al.  Introns in Gene Evolution , 2004, Genetica.

[11]  A. Hüttenhofer,et al.  RNomics: identification and function of small, non-messenger RNAs. , 2002, Current opinion in chemical biology.

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

[13]  Filomena Anna Digilio,et al.  A computational search for box C/D snoRNA genes in the Drosophila melanogaster genome , 2004, Bioinform..

[14]  J. Steitz,et al.  Guided tours: from precursor snoRNA to functional snoRNP. , 1999, Current opinion in cell biology.

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

[16]  Alexei Fedorov,et al.  Introns in gene evolution. , 2003 .

[17]  C. Daniels,et al.  Structure and function of archaeal box C/D sRNP core proteins , 2003, Nature Structural Biology.

[18]  Hui Zhou,et al.  Different expression strategy: multiple intronic gene clusters of box H/ACA snoRNA in Drosophila melanogaster. , 2004, Journal of molecular biology.

[19]  Hervé Seitz,et al.  Identification of 13 novel human modification guide RNAs. , 2003, Nucleic acids research.

[20]  M. Fournier,et al.  The small nucleolar RNAs. , 1995, Annual review of biochemistry.

[21]  A. Hüttenhofer,et al.  Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. , 2000, Proceedings of the National Academy of Sciences of the United States of America.