TY  - INPR
A1  - Boeynaems, Steven
A1  - Dorone, Yanniv
A1  - Marian, Anca
A1  - Shabardina, Victoria
A1  - Huang, Guozhong
A1  - Kim, Garam
A1  - Sanyal, Anushka
A1  - Şen, Nesli Ece
A1  - Docampo, Roberto
A1  - Ruiz-Trillo, Iñaki
A1  - Lasker, Keren
A1  - Auburger, Georg
A1  - Kabashi, Edor
A1  - Gitler, Aaron D.
T1  - Poly(A)-binding protein is an ataxin-2 chaperone that emulsifies biomolecular condensates
T2  - bioRxiv
N2  - Biomolecular condensation underlies the biogenesis of an expanding array of membraneless assemblies, including stress granules (SGs) which form under a variety of cellular stresses. Advances have been made in understanding the molecular grammar that dictates the behavior of a few key scaffold proteins that make up these phases but how the partitioning of hundreds of other SG proteins is regulated remains largely unresolved. While investigating the rules that govern the condensation of ataxin-2, a SG protein implicated in neurodegenerative disease, we unexpectedly identified a short 14aa sequence that acts as an ataxin-2 condensation switch and is conserved across the eukaryote lineage. We identify poly(A)-binding proteins as unconventional RNA-dependent chaperones that control this regulatory switch. Our results uncover a hierarchy of cis and trans interactions that fine-tune ataxin-2 condensation and reveal a new molecular function for ancient poly(A)-binding proteins as emulsifiers of biomolecular condensate proteins. These findings may inspire novel approaches to therapeutically target aberrant phases in disease.
KW  - phase separation
KW  - short linear motif
KW  - polyQ
KW  - protein aggregation
KW  - prion-like
KW  - stress granules
KW  - frontotemporal dementia
KW  - amyotrophic lateral sclerosis
KW  - spinocerebellar ataxia
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72926
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-729268
IS  - 2021.08.23.457426
ER  -