RPS25 is required for efficient RAN translation of C9orf72 and other neurodegenerative disease-associated nucleotide repeats

Nat Neurosci. 2019 Sep;22(9):1383-1388. doi: 10.1038/s41593-019-0455-7. Epub 2019 Jul 29.

Abstract

Nucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. Unconventional translation (RAN translation) of C9orf72 repeats generates dipeptide repeat proteins that can cause neurodegeneration. We performed a genetic screen for regulators of RAN translation and identified small ribosomal protein subunit 25 (RPS25), presenting a potential therapeutic target for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia and other neurodegenerative diseases caused by nucleotide repeat expansions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C9orf72 Protein / genetics*
  • DNA Repeat Expansion / genetics
  • Humans
  • Neurodegenerative Diseases / genetics*
  • Protein Biosynthesis
  • Ribosomal Proteins / genetics*

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • RPS25 protein, human
  • Ribosomal Proteins