Measuring Repeat-Associated Non-AUG (RAN) Translation

Shaopeng Wang, Shuying Sun

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Expansions of short nucleotide repeats account for more than 50 neurological or neuromuscular diseases. Many repeat expansion-containing RNAs can generate toxic repeat proteins through repeat-associated non-AUG (RAN) translation in all the reading frames. Understanding how RAN translation occurs and what cellular factors regulate this process will help decipher the basic mechanism of the molecular process and disease pathogenesis. Using reporter systems to quantitatively measure RAN translation provides a platform to examine candidate genes/pathways and screen for modifiers of this non-canonical pathway. In this chapter, we describe the dual-luciferase reporter system to measure RAN translation using C9ORF72 GGGGCCexp as an example, which is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages113-132
Number of pages20
DOIs
StatePublished - 2022

Publication series

NameMethods in Molecular Biology
Volume2428
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Cap-independent
  • Integrated stress response
  • RAN translation
  • Repeat expansion
  • eIF2α phosphorylation

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

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