Journal
NATURE CHEMICAL BIOLOGY
Volume 9, Issue 1, Pages 59-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.1120
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Funding
- Howard Hughes Medical Institute International Student Research Fellowship
- National Research Service Award postdoctoral fellowship [1F32GM099408-01]
- Damon Runyon-Rachleff Innovator Award
- Searle Scholars Award
- Richard and Susan Smith Family Foundation Fellowship
- Burroughs Wellcome Fund Career Award in Biomedical Sciences
- Alfred P. Sloan Fellowship
- US National Institutes of Health [T32GM007598]
- US National Human Genome Research Institute [3U54HG003067]
- Director's New Innovator Awards [DP2OD00667, DP2OD002374]
- National Institute of General Medical Sciences [R01GM102491]
- Harvard University
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U54HG003067] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM102491, F32GM099408, T32GM007598] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP2OD002374, DP2OD006670] Funding Source: NIH RePORTER
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The complete extent to which the human genome is translated into polypeptides is of fundamental importance. We report a peptidomic strategy to detect short open reading frame (sORF)-encoded polypeptides (SEPs) in human cells. We identify 90 SEPs, 86 of which are previously uncharacterized, which is the largest number of human SEPs ever reported. SEP abundances range from 10-1,000 molecules per cell, identical to abundances of known proteins. SEPs arise from sORFs in noncoding RNAs as well as multicistronic mRNAs, and many SEPs initiate with non-AUG start codons, indicating that noncanonical translation may be more widespread in mammals than previously thought. In addition, coding sORFs are present in a small fraction (8 out of 1,866) of long intergenic noncoding RNAs. Together, these results provide strong evidence that the human proteome is more complex than previously appreciated.
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