Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 3 May 2002:
Vol. 296. no. 5569, pp. 907 - 910
DOI: 10.1126/science.1069415
Prev | Table of Contents | Next

Reports

Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays

Tyson A. Clark,123 Charles W. Sugnet,234 Manuel Ares Jr.123*

Introns interrupt almost every eukaryotic protein-coding gene, yet how the splicing apparatus interprets the genome during messenger RNA (mRNA) synthesis is poorly understood. We designed microarrays to distinguish spliced from unspliced RNA for each intron-containing yeast gene and measured genomewide effects on splicing caused by loss of 18 different mRNA processing factors. After accommodating changes in transcription and decay by using gene-specific indexes, functional relationships between mRNA processing factors can be identified through their common effects on spliced and unspliced RNA. Groups of genes with different dependencies on mRNA processing factors are also apparent. Quantitative polymerase chain reactions confirm the array-based finding that Prp17p and Prp18p are not dispensable for removal of introns with short branchpoint-to-3' splice site distances.

1 Department of Molecular, Cell, and Developmental Biology,
2 Center for Molecular Biology of RNA, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA.
3 Center for Biomolecular Sciences and Engineering,
4 Department of Computer Sciences, Baskin School of Engineering, University of California, Santa Cruz, CA 95064, USA.
*   To whom correspondence should be addressed. E-mail: ares{at}biology.ucsc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Analysis of splicing patterns by pyrosequencing.
A. Mereau, V. Anquetil, M. Cibois, M. Noiret, A. Primot, A. Vallee, and L. Paillard (2009)
Nucleic Acids Res. 37, e126
   Abstract »    Full Text »    PDF »
Overestimation of alternative splicing caused by variable probe characteristics in exon arrays.
D. Gaidatzis, K. Jacobeit, E. J. Oakeley, and M. B. Stadler (2009)
Nucleic Acids Res. 37, e107
   Abstract »    Full Text »    PDF »
RiceArrayNet: A Database for Correlating Gene Expression from Transcriptome Profiling, and Its Application to the Analysis of Coexpressed Genes in Rice.
T.-H. Lee, Y.-K. Kim, T. T. M. Pham, S. I. Song, J.-K. Kim, K. Y. Kang, G. An, K.-H. Jung, D. W. Galbraith, M. Kim, et al. (2009)
Plant Physiology 151, 16-33
   Abstract »    Full Text »    PDF »
The cap binding complex influences H2B ubiquitination by facilitating splicing of the SUS1 pre-mRNA.
M. A. Hossain, J. M. Claggett, T. Nguyen, and T. L. Johnson (2009)
RNA 15, 1515-1527
   Abstract »    Full Text »    PDF »
Mutations in the U5 snRNA result in altered splicing of subsets of pre-mRNAs and reduced stability of Prp8.
C. J. Kershaw, J. D. Barrass, J. D. Beggs, and R. T. O'Keefe (2009)
RNA 15, 1292-1304
   Abstract »    Full Text »    PDF »
Current-generation high-throughput sequencing: deepening insights into mammalian transcriptomes.
B. J. Blencowe, S. Ahmad, and L. J. Lee (2009)
Genes & Dev. 23, 1379-1386
   Abstract »    Full Text »    PDF »
The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing.
M. Meyer and J. Vilardell (2009)
Brief Funct Genomic Proteomic
   Abstract »    Full Text »    PDF »
Sam68 Regulates a Set of Alternatively Spliced Exons during Neurogenesis.
G. Chawla, C.-H. Lin, A. Han, L. Shiue, M. Ares Jr., and D. L. Black (2009)
Mol. Cell. Biol. 29, 201-213
   Abstract »    Full Text »    PDF »
Determination of tag density required for digital transcriptome analysis: Application to an androgen-sensitive prostate cancer model.
H. Li, M. T. Lovci, Y.-S. Kwon, M. G. Rosenfeld, X.-D. Fu, and G. W. Yeo (2008)
PNAS 105, 20179-20184
   Abstract »    Full Text »    PDF »
MADS: A new and improved method for analysis of differential alternative splicing by exon-tiling microarrays.
Y. Xing, P. Stoilov, K. Kapur, A. Han, H. Jiang, S. Shen, D. L. Black, and W. H. Wong (2008)
RNA 14, 1470-1479
   Abstract »    Full Text »    PDF »
Arabidopsis Transcriptome Analysis under Drought, Cold, High-Salinity and ABA Treatment Conditions using a Tiling Array.
A. Matsui, J. Ishida, T. Morosawa, Y. Mochizuki, E. Kaminuma, T. A. Endo, M. Okamoto, E. Nambara, M. Nakajima, M. Kawashima, et al. (2008)
Plant Cell Physiol. 49, 1135-1149
   Abstract »    Full Text »    PDF »
Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay.
A. L. Saltzman, Y. K. Kim, Q. Pan, M. M. Fagnani, L. E. Maquat, and B. J. Blencowe (2008)
Mol. Cell. Biol. 28, 4320-4330
   Abstract »    Full Text »    PDF »
Splicing regulation: From a parts list of regulatory elements to an integrated splicing code.
Z. Wang and C. B. Burge (2008)
RNA 14, 802-813
   Abstract »    Full Text »    PDF »
Deletion of Many Yeast Introns Reveals a Minority of Genes that Require Splicing for Function.
J. Parenteau, M. Durand, S. Veronneau, A.-A. Lacombe, G. Morin, V. Guerin, B. Cecez, J. Gervais-Bird, C.-S. Koh, D. Brunelle, et al. (2008)
Mol. Biol. Cell 19, 1932-1941
   Abstract »    Full Text »    PDF »
Global analysis of mRNA splicing.
M. J. Moore and P. A. Silver (2008)
RNA 14, 197-203
   Abstract »    Full Text »    PDF »
Cwc24p, a Novel Saccharomyces cerevisiae Nuclear Ring Finger Protein, Affects Pre-snoRNA U3 Splicing.
M. B. Goldfeder and C. C. Oliveira (2008)
J. Biol. Chem. 283, 2644-2653
   Abstract »    Full Text »    PDF »
Regulation of Alternative Splicing: More than Just the ABCs.
A. E. House and K. W. Lynch (2008)
J. Biol. Chem. 283, 1217-1221
   Abstract »    Full Text »    PDF »
Genome-wide Analysis of Alternative Pre-mRNA Splicing.
C. Ben-Dov, B. Hartmann, J. Lundgren, and J. Valcarcel (2008)
J. Biol. Chem. 283, 1229-1233
   Abstract »    Full Text »    PDF »
Heritability of alternative splicing in the human genome.
T. Kwan, D. Benovoy, C. Dias, S. Gurd, D. Serre, H. Zuzan, T. A. Clark, A. Schweitzer, M. K. Staples, H. Wang, et al. (2007)
Genome Res. 17, 1210-1218
   Abstract »    Full Text »    PDF »
A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing.
D. Das, T. A. Clark, A. Schweitzer, M. Yamamoto, H. Marr, J. Arribere, S. Minovitsky, A. Poliakov, I. Dubchak, J. E. Blume, et al. (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons.
P. L. Boutz, P. Stoilov, Q. Li, C.-H. Lin, G. Chawla, K. Ostrow, L. Shiue, M. Ares Jr., and D. L. Black (2007)
Genes & Dev. 21, 1636-1652
   Abstract »    Full Text »    PDF »
Functional Characterization of Spliceosomal Introns and Identification of U2, U4, and U5 snRNAs in the Deep-Branching Eukaryote Entamoeba histolytica.
C. A. Davis, M. P. S. Brown, and U. Singh (2007)
Eukaryot. Cell 6, 940-948
   Abstract »    Full Text »    PDF »
Improving comparability between microarray probe signals by thermodynamic intensity correction.
G. M. Bruun, R. Wernersson, A. S. Juncker, H. Willenbrock, and H. B. Nielsen (2007)
Nucleic Acids Res. 35, e48
   Abstract »    Full Text »    PDF »
Genome-wide identification of spliced introns using a tiling microarray.
Z. Zhang, J. R. Hesselberth, and S. Fields (2007)
Genome Res. 17, 503-509
   Abstract »    Full Text »    PDF »
Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay.
J. Z. Ni, L. Grate, J. P. Donohue, C. Preston, N. Nobida, G. O'Brien, L. Shiue, T. A. Clark, J. E. Blume, and M. Ares Jr. (2007)
Genes & Dev. 21, 708-718
   Abstract »    Full Text »    PDF »
High-density yeast-tiling array reveals previously undiscovered introns and extensive regulation of meiotic splicing.
K. Juneau, C. Palm, M. Miranda, and R. W. Davis (2007)
PNAS 104, 1522-1527
   Abstract »    Full Text »    PDF »
ASEtrap: A biological method for speeding up the exploration of spliceomes.
G. Thill, V. Castelli, S. Pallud, M. Salanoubat, P. Wincker, P. de la Grange, D. Auboeuf, V. Schachter, and J. Weissenbach (2006)
Genome Res. 16, 776-786
   Abstract »    Full Text »    PDF »
Two-dimensional transcriptome profiling: identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens..
H.-R. Li, J. Wang-Rodriguez, T. M. Nair, J. M. Yeakley, Y.-S. Kwon, M. Bibikova, C. Zheng, L. Zhou, K. Zhang, T. Downs, et al. (2006)
Cancer Res. 66, 4079-4088
   Abstract »    Full Text »    PDF »
Inferring global levels of alternative splicing isoforms using a generative model of microarray data.
O. Shai, Q. D. Morris, B. J. Blencowe, and B. J. Frey (2006)
Bioinformatics 22, 606-613
   Abstract »    Full Text »    PDF »
Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae.
C. A. Davis and M. Ares Jr. (2006)
PNAS 103, 3262-3267
   Abstract »    Full Text »    PDF »
Proteomics of the Heart: Unraveling Disease.
E. McGregor and M. J. Dunn (2006)
Circ. Res. 98, 309-321
   Abstract »    Full Text »    PDF »
Cell Type and Culture Condition-Dependent Alternative Splicing in Human Breast Cancer Cells Revealed by Splicing-Sensitive Microarrays.
C. Li, M. Kato, L. Shiue, J. E. Shively, M. Ares Jr., and R.-J. Lin (2006)
Cancer Res. 66, 1990-1999
   Abstract »    Full Text »    PDF »
Prp43p Is a DEAH-Box Spliceosome Disassembly Factor Essential for Ribosome Biogenesis.
D. J. Combs, R. J. Nagel, M. Ares Jr., and S. W. Stevens (2006)
Mol. Cell. Biol. 26, 523-534
   Abstract »    Full Text »    PDF »
HOLLYWOOD: a comparative relational database of alternative splicing.
D. Holste, G. Huo, V. Tung, and C. B. Burge (2006)
Nucleic Acids Res. 34, D56-D62
   Abstract »    Full Text »    PDF »
The Protein Phosphatase AtPP2CA Negatively Regulates Abscisic Acid Signal Transduction in Arabidopsis, and Effects of abh1 on AtPP2CA mRNA.
J. M. Kuhn, A. Boisson-Dernier, M. B. Dizon, M. H. Maktabi, and J. I. Schroeder (2006)
Plant Physiology 140, 127-139
   Abstract »    Full Text »    PDF »
MAASE: An alternative splicing database designed for supporting splicing microarray applications.
C. L. ZHENG, Y.-S. KWON, H.-R. LI, K. ZHANG, G. COUTINHO-MANSFIELD, C. YANG, T. M. NAIR, M. GRIBSKOV, and X.-D. FU (2005)
RNA 11, 1767-1776
   Abstract »    Full Text »    PDF »
OligoWiz 2.0--integrating sequence feature annotation into the design of microarray probes.
R. Wernersson and H. B. Nielsen (2005)
Nucleic Acids Res. 33, W611-W615
   Abstract »    Full Text »    PDF »
Global analysis of positive and negative pre-mRNA splicing regulators in Drosophila.
M. Blanchette, R. E. Green, S. E. Brenner, and D. C. Rio (2005)
Genes & Dev. 19, 1306-1314
   Abstract »    Full Text »    PDF »
Global analysis of yeast RNA processing identifies new targets of RNase III and uncovers a link between tRNA 5' end processing and tRNA splicing.
S. L. Hiley, T. Babak, and T. R. Hughes (2005)
Nucleic Acids Res. 33, 3048-3056
   Abstract »    Full Text »    PDF »
Identifying differentially expressed genes from microarray experiments via statistic synthesis.
Y. H. Yang, Y. Xiao, and M. R. Segal (2005)
Bioinformatics 21, 1084-1093
   Abstract »    Full Text »    PDF »
Genetic and Functional Interaction of Evolutionarily Conserved Regions of the Prp18 Protein and the U5 snRNA.
D. Bacikova and D. S. Horowitz (2005)
Mol. Cell. Biol. 25, 2107-2116
   Abstract »    Full Text »    PDF »
A microarray configuration to quantify expression levels and relative abundance of splice variants.
P. Fehlbaum, C. Guihal, L. Bracco, and O. Cochet (2005)
Nucleic Acids Res. 33, e47
   Abstract »    Full Text »    PDF »
Alternative Splicing Microarrays Reveal Functional Expression of Neuron-specific Regulators in Hodgkin Lymphoma Cells.
A. Relogio, C. Ben-Dov, M. Baum, M. Ruggiu, C. Gemund, V. Benes, R. B. Darnell, and J. Valcarcel (2005)
J. Biol. Chem. 280, 4779-4784
   Abstract »    Full Text »    PDF »
Analysis of Mutant Phenotypes and Splicing Defects Demonstrates Functional Collaboration between the Large and Small Subunits of the Essential Splicing Factor U2AF In Vivo.
C. J. Webb, S. Lakhe-Reddy, C. M. Romfo, and J. A. Wise (2005)
Mol. Biol. Cell 16, 584-596
   Abstract »    Full Text »    PDF »
Detecting tissue-specific regulation of alternative splicing as a qualitative change in microarray data.
K. Le, K. Mitsouras, M. Roy, Q. Wang, Q. Xu, S. F. Nelson, and C. Lee (2004)
Nucleic Acids Res. 32, e180
   Abstract »    Full Text »    PDF »
Genome-wide Analysis of Pre-mRNA Splicing: INTRON FEATURES GOVERN THE REQUIREMENT FOR THE SECOND-STEP FACTOR, Prp17 IN SACCHAROMYCES CEREVISIAE AND SCHIZOSACCHAROMYCES POMBE.
A. K. Sapra, Y. Arava, P. Khandelia, and U. Vijayraghavan (2004)
J. Biol. Chem. 279, 52437-52446
   Abstract »    Full Text »    PDF »
A systems view of mRNP biology.
H. Hieronymus and P. A. Silver (2004)
Genes & Dev. 18, 2845-2860
   Abstract »    Full Text »    PDF »
The Saccharomyces cerevisiae gene CDC40/PRP17 controls cell cycle progression through splicing of the ANC1 gene.
O. Dahan and M. Kupiec (2004)
Nucleic Acids Res. 32, 2529-2540
   Abstract »    Full Text »    PDF »
An Arabidopsis RNA Lariat Debranching Enzyme Is Essential for Embryogenesis.
H. Wang, K. Hill, and S. E. Perry (2004)
J. Biol. Chem. 279, 1468-1473
   Abstract »    Full Text »    PDF »
Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays.
J. M. Johnson, J. Castle, P. Garrett-Engele, Z. Kan, P. M. Loerch, C. D. Armour, R. Santos, E. E. Schadt, R. Stoughton, and D. D. Shoemaker (2003)
Science 302, 2141-2144
   Abstract »    Full Text »    PDF »
Proteomics of heart disease.
E. McGregor and M. J. Dunn (2003)
Hum. Mol. Genet. 12, R135-144
   Abstract »    Full Text »    PDF »
Large scale study of protein domain distribution in the context of alternative splicing.
S. Liu and R. B. Altman (2003)
Nucleic Acids Res. 31, 4828-4835
   Abstract »    Full Text »    PDF »
SCNM1, a Putative RNA Splicing Factor That Modifies Disease Severity in Mice.
D. A. Buchner, M. Trudeau, and M. H. Meisler (2003)
Science 301, 967-969
   Abstract »    Full Text »    PDF »
Single Molecule Profiling of Alternative Pre-mRNA Splicing.
J. Zhu, J. Shendure, R. D. Mitra, and G. M. Church (2003)
Science 301, 836-838
   Abstract »    Full Text »    PDF »
Spatial Organization of Protein-RNA Interactions in the Branch Site-3' Splice Site Region during pre-mRNA Splicing in Yeast.
D. S. McPheeters and P. Muhlenkamp (2003)
Mol. Cell. Biol. 23, 4174-4186
   Abstract »    Full Text »    PDF »
Genome-wide analysis of mRNA translation profiles in Saccharomycescerevisiae.
Y. Arava, Y. Wang, J. D. Storey, C. L. Liu, P. O. Brown, and D. Herschlag (2003)
PNAS 100, 3889-3894
   Abstract »    Full Text »    PDF »
Alternative Splicing Modulation by a LAMMER Kinase Impinges on Developmental and Transcriptome Expression.
S. Savaldi-Goldstein, D. Aviv, O. Davydov, and R. Fluhr (2003)
PLANT CELL 15, 926-938
   Abstract »    Full Text »    PDF »
Dual Roles for Spt5 in Pre-mRNA Processing and Transcription Elongation Revealed by Identification of Spt5-Associated Proteins.
D. L. Lindstrom, S. L. Squazzo, N. Muster, T. A. Burckin, K. C. Wachter, C. A. Emigh, J. A. McCleery, J. R. Yates III, and G. A. Hartzog (2003)
Mol. Cell. Biol. 23, 1368-1378
   Abstract »    Full Text »    PDF »
Pre-mRNA splicing and human disease.
N. A. Faustino and T. A. Cooper (2003)
Genes & Dev. 17, 419-437
   Full Text »    PDF »
Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors.
M. ALBERS, A. DIMENT, M. MURARU, C. S. RUSSELL, and J. D. BEGGS (2003)
RNA 9, 138-150
   Abstract »    Full Text »    PDF »
Mutations in U5 snRNA loop 1 influence the splicing of different genes in vivo.
R. T. O'Keefe (2002)
Nucleic Acids Res. 30, 5476-5484
   Abstract »    Full Text »    PDF »
Mutations in genes of Saccharomyces cerevisiae encoding pre-mRNA splicing factors cause cell cycle arrest through activation of the spindle checkpoint.
O. Dahan and M. Kupiec (2002)
Nucleic Acids Res. 30, 4361-4370
   Abstract »    Full Text »    PDF »
Signals and their transduction pathways regulating alternative splicing: a new dimension of the human genome.
S. Stamm (2002)
Hum. Mol. Genet. 11, 2409-2416
   Abstract »    Full Text »    PDF »
Genome-wide detection of tissue-specific alternative splicing in the human transcriptome.
Q. Xu, B. Modrek, and C. Lee (2002)
Nucleic Acids Res. 30, 3754-3766
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)