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

Jongbo Lee1, Minjong Kim1, Taichi Q Itoh2

  • 1School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, South Korea.

Wiley Interdisciplinary Reviews. RNA
|June 6, 2018
PubMed
Summary

Ataxin-2 (ATXN2) protein regulates gene expression and neural functions. Loss-of-function in ATXN2 may offer therapeutic targets for neurodegenerative disorders.

Keywords:
Ataxin-2 (ATXN2)neural functionneurodegenerative diseasesposttranscriptional gene regulation

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Area of Science:

  • Molecular biology
  • Neuroscience
  • Genetics

Background:

  • Ataxin-2 (ATXN2) is a conserved RNA-binding protein implicated in neurodegenerative diseases.
  • While gain-of-function mutations are linked to disease, ATXN2 also has direct roles in neural function.

Purpose of the Study:

  • To explore the direct roles of ATXN2 in neural physiology.
  • To understand ATXN2's function in posttranscriptional gene regulation and neural homeostasis.
  • To investigate ATXN2's potential as a therapeutic target.

Main Methods:

  • Review of existing literature on ATXN2 function.
  • Analysis of ATXN2's role in RNA processing (poly-A tailing, stabilization, silencing, translation).
  • Examination of genetic models of ATXN2 loss-of-function.

Main Results:

  • ATXN2 controls key posttranscriptional events, including RNA stabilization and microRNA-dependent silencing.
  • ATXN2 influences neural processes like circadian rhythms and olfactory habituation.
  • Loss of ATXN2 impacts stress granules, mTOR signaling, and cellular metabolism, vital for neural homeostasis.

Conclusions:

  • ATXN2 acts as a crucial trans-acting module for posttranscriptional control in diverse neural functions.
  • The interaction of ATXN2 with neurodegenerative disease genes highlights its significance.
  • Targeting ATXN2 loss-of-function presents a potential therapeutic strategy for ATXN2-related neurological disorders.