ICTS:32841

Interplay between cellular homeostasis and protein aggregates

(2025). Interplay between cellular homeostasis and protein aggregates. SciVideos. https://scivideos.org/icts-tifr/32841

Interplay between cellular homeostasis and protein aggregates. SciVideos, Sep. 24, 2025, https://scivideos.org/icts-tifr/32841 

          @misc{ scivideos_ICTS:32841,
            doi = {},
            url = {https://scivideos.org/icts-tifr/32841},
            author = {},
            keywords = {},
            language = {en},
            title = {Interplay between cellular homeostasis and protein aggregates},
            publisher = {},
            year = {2025},
            month = {sep},
            note = {ICTS:32841 see, \url{https://scivideos.org/icts-tifr/32841}}
          }
Amanjot Singh
Talk numberICTS:32841
Source RepositoryICTS-TIFR

Abstract

Ataxin-2 is a translational control molecule mutated in spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS). While intrinsically disordered domains (IDRs) of Ataxin-2 (Atx2) facilitate mRNP condensation into granules, how IDRs work with structured domains to enable positive and negative regulation of target mRNAs remains unclear. Using TRIBE (Targets of RNA-Binding Proteins Identified by Editing) technology, we identified an extensive dataset of Atx2-target mRNAs in the Drosophila brain. Ataxin-2 interactions with AU-rich elements in 3’UTRs modulate stability/ turnover of a large fraction of these target mRNAs. Further genomic and cell biological analyses of Atx2 domain-deletions demonstrate that Atx2: (a) interacts closely with target mRNAs within mRNP granules; (b) contains distinct protein domains that drive or oppose RNP-granule assembly; and (c) has additional essential roles outside of mRNP granules. These findings increase understanding of neuronal translational control mechanisms and inform strategies for Ataxin-2-based interventions under development for neurodegenerative disease.