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

American Association for the Advancement of Science (AAAS) - Tập 296 Số 5569 - Trang 907-910 - 2002
Tyson A. Clark1,2,3, Charles W. Sugnet1,2,4, Manuel Ares1,2,3
1Center for Biomolecular Sciences and Engineering,
2Center for Molecular Biology of RNA, Sinsheimer Laboratories, University of California, Santa Cruz, CA 95064, USA
3Department of Molecular Cell and Developmental Biology
4Department of Computer Sciences, Baskin School of Engineering, University of California, Santa Cruz, CA 95064, USA.

Tóm tắt

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.

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Supplementary on Science Online at www.sciencemag.org/cgi/content/full/296/5569/907/DC1. Microarray data are available at the Gene Expression Omnibus (GEO) at www.ncbi.nlm.nih.gov/geo/ under accession numbers GSE34 and GSE35.

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Thanks go to H. Igel for technical assistance; and to J. DeRisi T. Ferea T. Furey G. Hartzog D. Haussler H. Heynecker R. Perriman T. Powers L. Shiue and R. Samaha for advice. Funding was provided by a W. M. Keck Foundation Grant to the Center for Molecular Biology of RNA by National Cancer Institute grant CA77813 to M.A. and D. Haussler and by NIH grant GM40478 to M.A. T.C. was supported by a University of California Biotechnology training grant and an NIH Training Grant. C.S. is a Predoctoral Fellow of the Howard Hughes Medical Institute.