Ataxin-2: A versatile posttranscriptional regulator and its implication in neural function

Jongbo Lee, Minjong Kim, Taichi Q. Itoh, Chunghun Lim

研究成果: Contribution to journalArticle査読

4 被引用数 (Scopus)

抄録

Ataxin-2 (ATXN2) is a eukaryotic RNA-binding protein that is conserved from yeast to human. Genetic expansion of a poly-glutamine tract in human ATXN2 has been implicated in several neurodegenerative diseases, likely acting through gain-of-function effects. Emerging evidence, however, suggests that ATXN2 plays more direct roles in neural function via specific molecular and cellular pathways. ATXN2 and its associated protein complex control distinct steps in posttranscriptional gene expression, including poly-A tailing, RNA stabilization, microRNA-dependent gene silencing, and translational activation. Specific RNA substrates have been identified for the functions of ATXN2 in aspects of neural physiology, such as circadian rhythms and olfactory habituation. Genetic models of ATXN2 loss-of-function have further revealed its significance in stress-induced cytoplasmic granules, mechanistic target of rapamycin signaling, and cellular metabolism, all of which are crucial for neural homeostasis. Accordingly, we propose that molecular evolution has been selecting the ATXN2 protein complex as an important trans-acting module for the posttranscriptional control of diverse neural functions. This explains how ATXN2 intimately interacts with various neurodegenerative disease genes, and suggests that loss-of-function effects of ATXN2 could be therapeutic targets for ATXN2-related neurological disorders. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications.

本文言語英語
論文番号e1488
ジャーナルWiley Interdisciplinary Reviews: RNA
9
6
DOI
出版ステータス出版済み - 11 1 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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