Exploring functional relationships between components of the gene expression machinery.
Eukaryotic gene expression requires the coordinated activity of many macromolecular machines including transcription factors and RNA polymerase, the spliceosome, mRNA export factors, the nuclear pore, the ribosome and decay machineries. Yeast carrying mutations in genes encoding components of these machineries were examined using microarrays to measure changes in both pre-mRNA and mRNA levels. We used these measurements as a quantitative phenotype to ask how steps in the gene expression pathway are functionally connected. A multiclass support vector machine was trained to recognize the gene expression phenotypes caused by these mutations. In several cases, unexpected phenotype assignments by the computer revealed functional roles for specific factors at multiple steps in the gene expression pathway. The ability to resolve gene expression pathway phenotypes provides insight into how the major machineries of gene expression communicate with each other.
Burckin
Todd
T
Department of Molecular, Cell & Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA.
Nagel
Roland
R
Mandel-Gutfreund
Yael
Y
Shiue
Lily
L
Clark
Tyson A
TA
Chong
Jean-Leon
JL
Chang
Tien-Hsien
TH
Squazzo
Sharon
S
Hartzog
Grant
G
Ares
Manuel
M
D000251:Adenosine Triphosphatases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D053487:DEAD-box RNA Helicases; D005095:Exoribonucleases / Q000235:genetics; D063326:Exosome Multienzyme Ribonuclease Complex; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology*; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009713:Nucleotidyltransferases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014176:Protein Biosynthesis / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D000098556:mRNA Guanylyltransferases
D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D009713:Nucleotidyltransferases; D000098556:mRNA Guanylyltransferases; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C492152:DED1 protein, S cerevisiae; C027900:RNA-dependent ATPase; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases