2. Academic Validation
  3. A human microprotein that interacts with the mRNA decapping complex

A human microprotein that interacts with the mRNA decapping complex

  • Nat Chem Biol. 2017 Feb;13(2):174-180. doi: 10.1038/nchembio.2249.
Nadia G D'Lima 1,  Jiao Ma 2,  Lauren Winkler 1,  Qian Chu 2,  Ken H Loh 3,  Elizabeth O Corpuz 4,  Bogdan A Budnik 5,  Jens Lykke-Andersen 4,  Alan Saghatelian 2,  Sarah A Slavoff 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Chemical Biology, Chemical Biology Institute, Yale University, New Haven, Connecticut, USA.
  • 2 Clayton Foundation Peptide Biology Lab, Helmsley Center for Genomic Medicine, Salk Institute for Biological Studies, La Jolla, California, USA.
  • 3 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • 4 Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
  • 5 FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
PMID: 27918561 DOI: 10.1038/nchembio.2249
Abstract

Proteomic detection of non-annotated microproteins indicates the translation of hundreds of small open reading frames (smORFs) in human cells, but whether these microproteins are functional or not is unknown. Here, we report the discovery and characterization of a 7-kDa human microprotein we named non-annotated P-body dissociating polypeptide (NoBody). NoBody interacts with mRNA decapping proteins, which remove the 5' cap from mRNAs to promote 5'-to-3' decay. Decapping proteins participate in mRNA turnover and nonsense-mediated decay (NMD). NoBody localizes to mRNA-decay-associated RNA-protein granules called P-bodies. Modulation of NoBody levels reveals that its abundance is anticorrelated with cellular P-body numbers and alters the steady-state levels of a cellular NMD substrate. These results implicate NoBody as a novel component of the mRNA decapping complex and demonstrate potential functionality of a newly discovered microprotein.

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