4.6 Article

Dynamics of T-Cell Intracellular Antigen 1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy under Oxidative Stress

Journal

CELLS
Volume 11, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/cells11050884

Keywords

TIA1; oxidative stress; stress granules; Welander distal myopathy

Categories

Funding

  1. Ministerio de Ciencia e Innovacion
  2. Agencia Espanola de Investigacion through FEDER funds [RTI2018-098517-B100]
  3. Fundacion Ramon Areces
  4. Banco Santander, Spain

Ask authors/readers for more resources

This study provides new insights into the role of TIA1 and WDM mutation in SG formation by analyzing the properties and dynamics of TIA1 protein and the formation/disassembly process of TIA1(WT/WDM)-dependent SGs.
T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is primarily involved in the post-transcriptional regulation of cellular RNAs. Furthermore, it is a key component of stress granules (SGs), RNA, and protein aggregates that are formed in response to stressful stimuli to reduce cellular activity as a survival mechanism. TIA1 p.E384K mutation is the genetic cause of Welander distal myopathy (WDM), a late-onset muscular dystrophy whose pathogenesis has been related to modifying SG dynamics. In this study, we present the results obtained by analyzing two specific aspects: (i) SGs properties and dynamics depending on the amino acid at position 384 of TIA1; and (ii) the formation/disassembly time-course of TIA1(WT/WDM)-dependent SGs under oxidative stress. The generation of TIA1 variants-in which the amino acid mutated in WDM and the adjacent ones were replaced by lysines, glutamic acids, or alanines-allowed us to verify that the inclusion of a single lysine is necessary and sufficient to alter SGs dynamics. Moreover, time-lapse microscopy analysis allowed us to establish in vivo the dynamics of TIA1(WT/WDM)-dependent SG formation and disassembly, after the elimination of the oxidizing agent, for 1 and 3 h, respectively. Our observations show distinct dynamics between the formation and disassembly of TIA1(WT/WDM)-dependent SGs. Taken together, this study has allowed us to expand the existing knowledge on the role of TIA1 and the WDM mutation in SG formation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available