Shedding Light on the Ghost Proteome

Trends Biochem Sci. 2021 Mar;46(3):239-250. doi: 10.1016/j.tibs.2020.10.003. Epub 2020 Nov 24.

Abstract

Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics has led to the identification of proteins translated from alternative open reading frames (AltORFs) in mRNAs. AltORFs are found in addition to predicted reference ORFs and noncoding RNA. Alternative proteins are not represented in the conventional protein databases, and this 'Ghost proteome' was not considered until recently. Some of these proteins are functional, and there is growing evidence that they are involved in central functions in physiological and physiopathological contexts. Here, we review how this Ghost proteome fills the gap in our understanding of signaling pathways, establishes new markers of pathologies, and highlights therapeutic targets.

Keywords: SEPs; alternative protein (AltProt); hidden proteome; mass spectrometry; smProt; small ORF (smORF).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Databases, Protein
  • Open Reading Frames
  • Protein Biosynthesis*
  • Proteome* / genetics
  • Proteomics

Substances

  • Proteome