Translation deregulation in human disease

Nat Rev Mol Cell Biol. 2018 Dec;19(12):791-807. doi: 10.1038/s41580-018-0034-x.


Advances in sequencing and high-throughput techniques have provided an unprecedented opportunity to interrogate human diseases on a genome-wide scale. The list of disease-causing mutations is expanding rapidly, and mutations affecting mRNA translation are no exception. Translation (protein synthesis) is one of the most complex processes in the cell. The orchestrated action of ribosomes, tRNAs and numerous translation factors decodes the information contained in mRNA into a polypeptide chain. The intricate nature of this process renders it susceptible to deregulation at multiple levels. In this Review, we summarize current evidence of translation deregulation in human diseases other than cancer. We discuss translation-related diseases on the basis of the molecular aberration that underpins their pathogenesis (including tRNA dysfunction, ribosomopathies, deregulation of the integrated stress response and deregulation of the mTOR pathway) and describe how deregulation of translation generates the phenotypic variability observed in these disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Variation, Population / genetics
  • Disease / genetics*
  • Humans
  • Peptide Initiation Factors / genetics
  • Protein Biosynthesis / genetics*
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / genetics
  • RNA, Transfer / genetics
  • Ribosomes / genetics
  • Stress, Physiological / genetics
  • TOR Serine-Threonine Kinases / genetics


  • Peptide Initiation Factors
  • RNA, Messenger
  • RNA, Transfer
  • MTOR protein, human
  • TOR Serine-Threonine Kinases