A Panoramic View of Yeast Noncoding RNA Processing

Predictive analysis using publicly available yeast functional genomics and proteomics data suggests that many more proteins may be involved in biogenesis of ribonucleoproteins than are currently known. Using a microarray that monitors abundance and processing of noncoding RNAs, we analyzed 468 yeast strains carrying mutations in protein-coding genes, most of which have not previously been associated with RNA or RNP synthesis. Many strains mutated in uncharacterized genes displayed aberrant noncoding RNA profiles. Ten factors involved in noncoding RNA biogenesis were verified by further experimentation, including a protein required for 20S pre-rRNA processing (Tsr2p), a protein associated with the nuclear exosome (Lrp1p), and a factor required for box C/D snoRNA accumulation (Bcd1p). These data present a global view of yeast noncoding RNA processing and confirm that many currently uncharacterized yeast proteins are involved in biogenesis of noncoding RNA.

[1]  Gary D Bader,et al.  Analyzing yeast protein–protein interaction data obtained from different sources , 2002, Nature Biotechnology.

[2]  H. Tschochner,et al.  The pre-ribosomal network. , 2003, Nucleic acids research.

[3]  Y. Kikuchi,et al.  Yeast Krr1p Physically and Functionally Interacts with a Novel Essential Kri1p, and Both Proteins Are Required for 40S Ribosome Biogenesis in the Nucleolus , 2000, Molecular and Cellular Biology.

[4]  P. Mitchell,et al.  Functions of the exosome in rRNA, snoRNA and snRNA synthesis , 1999, The EMBO journal.

[5]  S. P. Fodor,et al.  Large-Scale Transcriptional Activity in Chromosomes 21 and 22 , 2002, Science.

[6]  Z. Strezoska,et al.  ERB1, the yeast homolog of mammalian Bop1, is an essential gene required for maturation of the 25S and 5.8S ribosomal RNAs. , 2001, Nucleic acids research.

[7]  Bernhard Kuster,et al.  90S pre-ribosomes include the 35S pre-rRNA, the U3 snoRNP, and 40S subunit processing factors but predominantly lack 60S synthesis factors. , 2002, Molecular cell.

[8]  M. Mann,et al.  Directed Proteomic Analysis of the Human Nucleolus , 2002, Current Biology.

[9]  Dmitrij Frishman,et al.  MIPS: a database for genomes and protein sequences , 1999, Nucleic Acids Res..

[10]  E. Phizicky,et al.  A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine modification of tRNA. , 2002, RNA.

[11]  C. Ball,et al.  Saccharomyces Genome Database. , 2002, Methods in enzymology.

[12]  T. Pederson,et al.  The plurifunctional nucleolus. , 1998, Nucleic acids research.

[13]  P. Bork,et al.  Functional organization of the yeast proteome by systematic analysis of protein complexes , 2002, Nature.

[14]  J. Shabanowitz,et al.  A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis , 2002, Nature.

[15]  R. Parker,et al.  Three conserved members of the RNase D family have unique and overlapping functions in the processing of 5S, 5.8S, U4, U5, RNase MRP and RNase P RNAs in yeast , 2000, The EMBO journal.

[16]  Mark D. Robinson,et al.  FunSpec: a web-based cluster interpreter for yeast , 2002, BMC Bioinformatics.

[17]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[18]  David G. Stork,et al.  Pattern Classification , 1973 .

[19]  R. Stoughton,et al.  Experimental annotation of the human genome using microarray technology , 2001, Nature.

[20]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  P. Grandi,et al.  Identification of a 60S preribosomal particle that is closely linked to nuclear export. , 2001, Molecular cell.

[22]  S. Colowick,et al.  Methods in Enzymology , Vol , 1966 .

[23]  Lani F. Wu,et al.  Large-scale prediction of Saccharomyces cerevisiae gene function using overlapping transcriptional clusters , 2002, Nature Genetics.

[24]  David G. Stork,et al.  Pattern classification, 2nd Edition , 2000 .

[25]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[26]  K. Entian,et al.  The essential protein Fap7 is involved in the oxidative stress response of Saccharomyces cerevisiae , 2000, Molecular microbiology.

[27]  Tyson A. Clark,et al.  Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays , 2002, Science.

[28]  A. Fatica,et al.  Purified Box C/D snoRNPs Are Able To Reproduce Site-Specific 2′-O-Methylation of Target RNA In Vitro , 2002, Molecular and Cellular Biology.

[29]  David Tollervey,et al.  60S pre‐ribosome formation viewed from assembly in the nucleolus until export to the cytoplasm , 2002, The EMBO journal.

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

[31]  Franco Cerrina,et al.  Gene expression analysis using oligonucleotide arrays produced by maskless photolithography. , 2002, Genome research.

[32]  P. Gleizes,et al.  Nog2p, a putative GTPase associated with pre‐60S subunits and required for late 60S maturation steps , 2001, The EMBO journal.

[33]  A. Fatica,et al.  Yeast snoRNA accumulation relies on a cleavage‐dependent/polyadenylation‐independent 3′‐processing apparatus , 2000, The EMBO journal.

[34]  D Haussler,et al.  Knowledge-based analysis of microarray gene expression data by using support vector machines. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Christopher M. Bishop,et al.  Neural networks for pattern recognition , 1995 .

[36]  S. Eddy.  Computational Genomics of Noncoding RNA Genes , 2002, Cell.

[37]  M Aldea,et al.  A Set of Vectors with a Tetracycline‐Regulatable Promoter System for Modulated Gene Expression in Saccharomyces cerevisiae , 1997, Yeast.

[38]  M. Mann,et al.  The Exosome: A Conserved Eukaryotic RNA Processing Complex Containing Multiple 3′→5′ Exoribonucleases , 1997, Cell.

[39]  Patrick Linder,et al.  Protein trans-Acting Factors Involved in Ribosome Biogenesis in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[40]  J. Shabanowitz,et al.  Composition and functional characterization of yeast 66S ribosome assembly intermediates. , 2001, Molecular cell.

[41]  S. Eddy.  Non–coding RNA genes and the modern RNA world , 2001, Nature Reviews Genetics.

[42]  R. Gromadka,et al.  The KRR1 gene encodes a protein required for 18S rRNA synthesis and 40S ribosomal subunit assembly in Saccharomyces cerevisiae. , 2000, Acta biochimica Polonica.

[43]  D. Tollervey,et al.  Ribosome synthesis in Saccharomyces cerevisiae. , 1999, Annual review of genetics.

[44]  P. Legrain,et al.  Yeast RNase III as a key processing enzyme in small nucleolar RNAs metabolism. , 1998, Journal of molecular biology.

[45]  David Tollervey,et al.  Making ribosomes. , 2002, Current opinion in cell biology.

[46]  G. Fink,et al.  Methods in enzymology vol 194 guide to yeast genetics and molecular biology , 1991 .

[47]  D. Tollervey,et al.  Yeast Rnt1p is required for cleavage of the pre-ribosomal RNA in the 3' ETS but not the 5' ETS. , 1999, RNA.

[48]  Yudong D. He,et al.  Functional Discovery via a Compendium of Expression Profiles , 2000, Cell.

[49]  D. Tollervey,et al.  Naf1 p is a box H/ACA snoRNP assembly factor. , 2002, RNA.

[50]  B. Séraphin,et al.  A generic protein purification method for protein complex characterization and proteome exploration , 1999, Nature Biotechnology.

[51]  A. Hopper,et al.  The yeast RNA1 gene product necessary for RNA processing is located in the cytosol and apparently excluded from the nucleus , 1990, The Journal of cell biology.

[52]  D. Dorris,et al.  Quantitative assessment of the use of modified nucleoside triphosphates in expression profiling: differential effects on signal intensities and impacts on expression ratios , 2002, BMC biotechnology.

[53]  Michael W. Briggs,et al.  Rrp6p, the Yeast Homologue of the Human PM-Scl 100-kDa Autoantigen, Is Essential for Efficient 5.8 S rRNA 3′ End Formation* , 1998, The Journal of Biological Chemistry.

[54]  D. Tollervey,et al.  Box C/D small nucleolar RNA trafficking involves small nucleolar RNP proteins, nucleolar factors and a novel nuclear domain , 2001, The EMBO journal.

[55]  David Penny,et al.  Relics from the RNA World , 1998, Journal of Molecular Evolution.

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

[57]  Terence P. Speed,et al.  Normalization for cDNA microarry data , 2001, SPIE BiOS.

[58]  A. Marchfelder,et al.  The final cut , 2001 .

[59]  David Botstein,et al.  SGD: Saccharomyces Genome Database , 1998, Nucleic Acids Res..

[60]  J. Boeke,et al.  Isolation and characterization of the gene encoding yeast debranching enzyme , 1991, Cell.

[61]  B. Bilican,et al.  Saccharomyces cerevisiae C1D is implicated in both non‐homologous DNA end joining and homologous recombination , 2002, Molecular microbiology.

[62]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[63]  M. Gerstein,et al.  Subcellular localization of the yeast proteome. , 2002, Genes & development.

[64]  D. Gelperin,et al.  Bms1p, a novel GTP-binding protein, and the related Tsr1p are required for distinct steps of 40S ribosome biogenesis in yeast. , 2001, RNA.

[65]  Sherif Abou Elela,et al.  RNase III Cleaves Eukaryotic Preribosomal RNA at a U3 snoRNP-Dependent Site , 1996, Cell.

[66]  Y. Tone,et al.  Nob1p is required for biogenesis of the 26S proteasome and degraded upon its maturation in Saccharomyces cerevisiae. , 2002, Genes & development.

[67]  S. Dudoit,et al.  Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. , 2002, Nucleic acids research.

[68]  T. Mélèse,et al.  NSR1 is required for pre-rRNA processing and for the proper maintenance of steady-state levels of ribosomal subunits , 1992, Molecular and cellular biology.

[69]  F. Sherman.  Getting started with yeast. , 1991, Methods in enzymology.

[70]  D. Tollervey,et al.  Ssf1p prevents premature processing of an early pre-60S ribosomal particle. , 2002, Molecular cell.

[71]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[72]  G. Cagney,et al.  RNA Polymerase II Elongation Factors of Saccharomyces cerevisiae: a Targeted Proteomics Approach , 2002, Molecular and Cellular Biology.

[73]  N. Lee,et al.  A concise guide to cDNA microarray analysis. , 2000, BioTechniques.

[74]  Yudong D. He,et al.  Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer , 2001, Nature Biotechnology.