A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining

Slavoff, Sarah A.; Heo, Jun; Budnik, Bogdan; Hanakahi, Leslyn A.; Saghatelian, Alan

doi:10.1074/jbc.c113.533968

Cited by 142 publications

(155 citation statements)

References 41 publications

(34 reference statements)

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“…Therefore, we hypothesized that MRI-2-SEP may also play a role in NHEJ pathway through protein-protein interactions with the Ku70/Ku80 heterodimer. Subsequent studies confirmed this assumption and showed that MRI-2 accumulates in the nucleus upon Ku overexpression and induction of DSBs, and enhances the rate of NHEJ in vitro (Slavoff et al, 2014) (Figure 5). Last but not least, gene expression profiling is also a useful tool to analyze and elucidate SEP functions.…”

Section: Mechanistic Investigationmentioning

confidence: 75%

Identification and characterization of sORF-encoded polypeptides

Chu

Saghatelian

2015

Critical Reviews in Biochemistry and Molecular Biology

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Molecular biology, genomics and proteomics methods have been utilized to reveal a non-annotated class of endogenous polypeptides (small proteins and peptides) encoded by short open reading frames (sORFs), or small open reading frames (smORFs). We refer to these polypeptides as s(m)ORF-encoded polypeptides or SEPs. The early SEPs were identified via genetic screens, and many of the RNAs that contain s(m)ORFs were originally considered to be non-coding; however, elegant work in bacteria and flies demonstrated that these s(m)ORFs code for functional polypeptides as small as 11-amino acids in length. The discovery of these initial SEPs led to searches for these molecules using methods such as ribosome profiling and proteomics, which have revealed the existence of many SEPs, including novel human SEPs. Unlike screens, –omics methods do not necessarily link a SEP to a cellular or biological function, but functional genomic and proteomic strategies have demonstrated that at least some of these newly discovered SEPs have biochemical and cellular functions. Here, we provide an overview of these results and discuss the future directions in this emerging field.

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Section: Mechanistic Investigationmentioning

confidence: 75%

Identification and characterization of sORF-encoded polypeptides

Chu

Saghatelian

2015

Critical Reviews in Biochemistry and Molecular Biology

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“…The human 24-aa humanin exerts its effect by binding to a heterotrimeric receptor [7] and regulates Bax during apoptosis by interacting and preventing Bax's translocation from the cytosol to mitochondria. The small protein MRI-2 also acts in a similar fashion in DNA repair [15]. Similar small proteins that contain protein-protein interaction domains and that regulate the assembly of functional protein complexes have been termed microproteins, by analogy with the action of microRNAs on mRNAs [16,17].…”

Section: Big Roles For Small Proteinsmentioning

confidence: 99%

Found in translation: functions and evolution of a recently discovered alternative proteome

Landry

Zhong

Nielly‐Thibault

et al. 2015

Current Opinion in Structural Biology

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“…MRI-2 was identified by proteomics and is a shorter isoform of the 156 amino acid MRI-1 gene 72 . MRI-1 was identified as a regulator of retroviral but its molecular mechanism was unknown.…”

Section: Potential Opportunities For Chemical Biologymentioning

confidence: 99%

Discovery and characterization of smORF-encoded bioactive polypeptides

2015

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Analysis of genomes, transcriptomes, and proteomes reveals the existence of hundreds to thousands of translated, yet non-annotated short open reading frames (small ORFs or smORFs). The discovery of smORFs, and their protein products, smORF-encoded polypeptides (SEPs), reveals a fundamental gap in our knowledge of protein-coding genes. Different studies have identified central roles for smORFs in metabolism, apoptosis, and development. The discovery of these bioactive SEPs emphasizes the functional potential of this unexplored class of biomolecules. Here, we provide an overview of this emerging field and highlight the opportunities for chemical biology to answer fundamental questions about these novel genes. Such studies will provide new insights into the protein-coding potential of genomes and identify functional genes with roles in biology and disease.

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A Human Short Open Reading Frame (sORF)-encoded Polypeptide That Stimulates DNA End Joining

Cited by 142 publications

References 41 publications

Identification and characterization of sORF-encoded polypeptides

Identification and characterization of sORF-encoded polypeptides

Found in translation: functions and evolution of a recently discovered alternative proteome

Discovery and characterization of smORF-encoded bioactive polypeptides

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