Quantitative profiling of peptides from RNAs classified as noncoding
Abstract
Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences—including introns and several classes of noncoding RNAs (ncRNAs)—do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here we use computational methods to identify the products of non-canonical translation in mouse neurons by analysing unannotated transcripts in combination with proteomic data. This study supports the existence of non-canonical translation products from both intragenic and extragenic genomic regions, including peptides derived from antisense transcripts and introns. Moreover, the studied novel translation products exhibit temporal regulation similar to that of proteins known to be involved in neuronal activity processes. These observations highlight a potentially large and complex set of biologically regulated translational events from transcripts formerly thought to lack coding potential.
Additional Information
© 2014 Macmillan Publishers Limited. Received 28 May 2014 | Accepted 30 Sep 2014 | Published 18 Nov 2014. S.P. and J.G. were supported in part by NSF 0856285. C.D. was supported by a Novartis fellowship and R.Y.T.-C. was supported by a Swiss National Science Foundation (SNF) Advanced Researcher Fellowship. D.W. was supported by the German Academic Exchange service and by an OFD grant to J.A.S. from HMS. H.S. was funded by R01GM094844. This work was funded in part by NIH NINDS R01 NS066973-04 to J.A.S. We would like to thank Erik Hemberg, Joseph Dexter and Anders Ståhlberg for helpful comments on the manuscript. We would like to thank Dr Sasha Singh in the Department of Cardiology at the Brigham and Women's Hospital and Dr John Asara at the BIDMC for the use of their Velos instruments. Contributions: S.P. designed and performed the final mass spectrometry and bioinformatics experiments, analysed the data and wrote the manuscript; M.H. developed concept, designed and carried out bioinformatics data analysis and wrote the manuscript; R.C. designed and carried out mass spectrometry validation experiments, molecular biology and biochemistry follow-up experiments and wrote the manuscript; D.W. designed and carried out the quantitative proteomics experiments; R.Y.T.-C. carried out initial pilot experiments and tested strategies; C.D. designed and performed initial neurobiology experiments; E.H. designed and performed initial neurobiological experiments; H.S. contributed to the mass spectrometric experiments and critically evaluated the data; J.G. contributed to the conceptual design and critically evaluated the results; G.K. developed the concept, supervised the RNA-seq part of the project and wrote the manuscript; and J.S. developed the concept, designed initial experiment, supervised the proteomics part of the project and wrote the manuscript. The authors declare no competing financial interests.Attached Files
Accepted Version - nihms632590.pdf
Supplemental Material - ncomms6429-s1.pdf
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Additional details
- PMCID
- PMC4416701
- Eprint ID
- 60781
- DOI
- 10.1038/ncomms6429
- Resolver ID
- CaltechAUTHORS:20151005-153440112
- 0856285
- NSF
- Novartis
- Swiss National Science Foundation (SNSF)
- Deutscher Akademischer Austauschdienst (DAAD)
- Harvard Medical School
- R01GM094844
- NIH
- R01 NS066973-04
- National Institute of Neurological Disorders and Stroke (NINDS)
- Created
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2015-10-06Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field