Observation of dually decoded regions of the human genome using ribosome profiling data
- Audrey M. Michel1,
- Kingshuk Roy Choudhury2,
- Andrew E. Firth3,
- Nicholas T. Ingolia4,
- John F. Atkins5,6 and
- Pavel V. Baranov1,7
- 1Biochemistry Department,
- 2Department of Statistics, University College Cork, Ireland;
- 3Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom;
- 4Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland 21218, USA;
- 5Biosciences Institute, University College Cork, Ireland;
- 6Human Genetics Department, University of Utah, Salt Lake City, Utah 84112, USA
Abstract
The recently developed ribosome profiling technique (Ribo-Seq) allows mapping of the locations of translating ribosomes on mRNAs with subcodon precision. When ribosome protected fragments (RPFs) are aligned to mRNA, a characteristic triplet periodicity pattern is revealed. We utilized the triplet periodicity of RPFs to develop a computational method for detecting transitions between reading frames that occur during programmed ribosomal frameshifting or in dual coding regions where the same nucleotide sequence codes for multiple proteins in different reading frames. Application of this method to ribosome profiling data obtained for human cells allowed us to detect several human genes where the same genomic segment is translated in more than one reading frame (from different transcripts as well as from the same mRNA) and revealed the translation of hitherto unpredicted coding open reading frames.
Footnotes
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↵7 Corresponding author
Email p.baranov{at}ucc.ie
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.133249.111.
Freely available online through the Genome Research Open Access option.
- Received October 12, 2011.
- Accepted May 8, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
