Person:
Ma, Jiao

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Ma

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Jiao

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Ma, Jiao

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Now showing 1 - 3 of 3
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    Publication
    Peptidomic discovery of short open reading frame-encoded peptides in human cells
    (2013) Slavoff, Sarah A.; Mitchell, Andrew J.; Schwaid, Adam G.; Cabili, Moran N.; Ma, Jiao; Levin, Joshua Z.; Karger, Amir; Budnik, Bogdan A.; Rinn, John; Saghatelian, Alan
    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.
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    Discovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue
    (American Chemical Society, 2014) Ma, Jiao; Ward, Carl; Jungreis, Irwin; Slavoff, Sarah A.; Schwaid, Adam G.; Neveu, John; Budnik, Bogdan; Kellis, Manolis; Saghatelian, Alan
    The existence of nonannotated protein-coding human short open reading frames (sORFs) has been revealed through the direct detection of their sORF-encoded polypeptide (SEP) products. The discovery of novel SEPs increases the size of the genome and the proteome and provides insights into the molecular biology of mammalian cells, such as the prevalent usage of non-AUG start codons. Through modifications of the existing SEP-discovery workflow, we discover an additional 195 SEPs in K562 cells and extend this methodology to identify novel human SEPs in additional cell lines and human tissue for a final tally of 237 new SEPs. These results continue to expand the human genome and proteome and demonstrate that SEPs are a ubiquitous class of nonannotated polypeptides that require further investigation.
  • Publication
    Discovery and Characterization of Novel smORF-Encoded Polypeptides (SEPs)
    (2016-01-04) Ma, Jiao; Saghatelian, Alan; Liu, David; Schreiber, Stuart L.
    Peptides and small proteins have essential physiological roles including metabolism (insulin), sleep (orexin), and stress (corticotropin-releasing hormone). Recent exploration of the human genome and proteome has revealed the existence of hundreds to thousands of short open reading frames (sORFs); however, the extent to which sORFs are translated into polypeptides is unknown. Inline with the current convention, a protein-coding short ORF is defined to be a small ORF or smORF; the protein product as a smORF-encoded polypeptide is called a SEP; and a sORF or smORF upstream from an open reading frame (i.e. in the 5’-UTR) is called an upstream ORF or uORF. The identification of smORFs and SEPs have prompted efforts determine the regulation and biological functions for these molecules. My thesis research focused on improving SEP discovery and the characterization of functional SEPs. The discovery of novel SEPs contributes to our understanding of composition of the human genome and proteome. My colleagues and I developed and utilized a proteogenomics strategy, which integrates genomics (RNA-Seq) with proteomics, to discover 86 novel human SEPs, the largest number of validated SEPs described at the time. Our findings indicated that SEPs are a large, unappreciated, peptide family. Moreover, our approach was far from optimized and we felt that there were likely many additional SEPs in the human genome. One goal of my thesis work was to improve the SEP discovery methodology to find more human SEPs. My efforts led to the discovery of an over 300 SEPs in cell lines and human tissue. A second goal of my thesis work was to identify and characterize functional SEPs. To do this I identified the SEPs that are most highly conserved throughout evolution with a program called PhyloCSF. PhyloCSF identifies which SEPs are evolutionary conserved to provide evidence for function. Seven out of the 300 plus SEPs had PhyloCSF scores that indicate that they have been conserved throughout evolution. These seven SEPs included an interesting SEP called SLC35A4-SEP that is generated from a uORF in the SLC35A4 gene. The SLC35A4-SEP had contained a transmembrane domain and analysis of cells revealed the mitochondrial localization of this SEP. Further characterization of SCL35A4 indicated that this polypeptide interacts with members of the ATP synthase complex. Though this interaction requires further validation the putative interactions suggested a role for SLC35A4-SEP in cellular energetics. Overexpression or knockout of SLC35A4-SEP affected cellular respiration. Ongoing work is testing to see if SLC35A4-SEP also effects mitochondrial membrane potential and structure of ATP-synthase. More generally, this approach highlights how I can begin to identify functional SEPs using a combination of computational and experimental methods. And my work on another functional SEP called NoBody indicates that this strategy is general.