title: Peptidomic discovery of short open reading frame-encoded peptides in human cells.
abstract: 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.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Slavoff
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mitchell
authors.forename: Adam G
authors.initials: AG
authors.lastname: Schwaid
authors.forename: Moran N
authors.initials: MN
authors.lastname: Cabili
authors.forename: Jiao
authors.initials: J
authors.lastname: Ma
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Levin
authors.forename: Amir D
authors.initials: AD
authors.lastname: Karger
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Budnik
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
authors.forename: Alan
authors.initials: A
authors.lastname: Saghatelian
mesh_terms: D003062:Codon; D006801:Humans; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry*; D020543:Proteome; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D003062:Codon; D010455:Peptides; D020543:Proteome; D012333:RNA, Messenger