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Published Online May 1, 2008
Science DOI: 10.1126/science.1158441

Reports

Submitted on March 31, 2008
Accepted on April 22, 2008

The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing

Ugrappa Nagalakshmi 1{dagger}, Zhong Wang 1{dagger}, Karl Waern 1, Chong Shou 2, Debasish Raha 1, Mark Gerstein 3, Michael Snyder 4*

1 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
2 Program in Computer Science & Computational Biology, Yale University, New Haven, CT 06520, USA.
3 Program in Computer Science & Computational Biology, Yale University, New Haven, CT 06520, USA.; Department of Molecular, Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
4 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.; Program in Computer Science & Computational Biology, Yale University, New Haven, CT 06520, USA.; Department of Molecular, Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.

* To whom correspondence should be addressed.
Michael Snyder , E-mail: michael.snyder{at}yale.edu

{dagger}These authors contributed equally to this work.

The identification of untranslated regions (UTRs), introns, and coding regions within an organism remains challenging. We developed a quantitative sequencing-based method for mapping transcribed regions called RNA-Seq in which cDNA fragments are subjected to high throughput sequencing and mapped to the genome. We applied RNA-Seq to generate a high-resolution transcriptome map of the yeast genome and demonstrated that most (74.5%) of the nonrepetitive sequence of the yeast genome is transcribed. We confirmed many known and predicted introns and demonstrated that others are not actively used. Alternative initiation codons and upstream open reading frames were also identified for many yeast genes. We also found unexpected 3’ end heterogeneity and the presence of many overlapping genes. These results indicate that the yeast transcriptome is more complex than previously appreciated.


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