Peptidomic discovery of short open reading frame-encoded peptides in human cells

By Sarah A. Slavoff, Andrew J. Mitchell, Adam G Schwaid, M. Cabili, Jiao Ma, J. Levin, Amir Karger, B. Budnik, Johannes Rinn, A. Saghatelian. Nature Chemical Biology, 2012

606 citations recorded by the source corpus.

The amount of the transcriptome that is translated into polypeptides is of fundamental importance. We developed a peptidomic strategy to detect short ORF (sORF)-encoded polypeptides (SEPs) in human cells. We identified 90 SEPs, 86 of which are novel, the largest number of human SEPs ever reported. SEP abundances range from 10-1000 molecules per cell, identical to known proteins. SEPs arise from sORFs in non-coding RNAs as well as multi-cistronic mRNAs, and many SEPs initiate with non-AUG start codons, indicating that non-canonical translation may be more widespread in mammals than previously thought. In addition, coding sORFs are present in a small fraction (8/1866) of long intergenic non-coding RNAs (lincRNAs). Together, these results provide the strongest evidence to date that the human proteome is more complex than previously appreciated.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/24505993c1240a012370a60131314f5df8cbee38

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Citations in the corpus

Proteogenomics: concepts, applications, and computational strategies (2014, background): “Although ribosome profiling and conventional RNA-seq demonstrate the protein-coding potential of these sORFs, prote-ogenomics provides additional evidence for the production of a stable protein product encoded by them 12,64,65 .”
Ribosome profiling provides evidence that large non-coding RNAs do not encode proteins (2013, methodology): “…(Derrien et al., 2012); (4) many physically interact with chromatin regulatory proteins to affect gene expression (Guttman et al., 2011; Guttman and Rinn, 2012; Wang and Chang, 2011); and (5) they rarely produce proteins detectable by mass spectrometry (Bánfai et al., 2012; Slavoff et al., 2013).”
Historical perspective of peptidomics (2014, background): “[140] Slavoff SA, Mitchell AJ, Schwaid AG, Cabili MN, Ma J, Levin JZ, et al.”
A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. (2015, background): “%) of encoding short ORF encoded polypeptides (Slavoff et al., 2013), NKILA does not have a typical protein-coding ORF that is longer than 300 nt. Confocal microscopy for fluorescent in situ hybridization (FISH) showed that NKILA located primarily in the cytoplasm (Figure 1B), which was confirmed…”
The Mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (2015, positive): “, 2006) and mammals (Frith et al., 2006; Slavoff et al., 2013), largely owing to technological advances that enable their detection and analysis.”
lincRNAs: Genomics, Evolution, and Mechanisms (2013, neutral): “4%) of the lincRNAs expressed in the human K562 cell line, and the extent to which even these peptides are functional is unknown (Slavoff et al., 2013).”
Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation (2014, background): “…(including lincRNAs) (Khalil et al , 2009; Guttman et al , 2010; Ingolia et al , 2011) contain multiple putative small open reading frames (smORFs, ≤ 100 aa) that can potentially be translated and thus might have a coding function (Ingolia et al , 2011; Chew et al , 2013; Slavoff et al , 2013).”