{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Linsenmeier M"],"funding":["NIA NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["RNA-binding proteins (RBPs) with prion-like domains, including FUS, hnRNPA1, and hnRNPA2, assemble into functional, metastable condensates that organize ribostasis, but can also transition into self-templating fibrils implicated in neurodegenerative proteinopathies such as amyotrophic lateral sclerosis (ALS). How nuclear-import receptors (NIRs) antagonize this pathological transition has remained unresolved. Here, we establish that NIRs regulate the phase behavior of prion-like cargos by remodeling the dilute phase. Quantitative analyses across length scales reveal that Karyopherin-β2 (Kapβ2) preferentially binds cargo in the dilute phase to lower the effective concentration of free RBPs thereby elevating the saturation concentration for phase separation and suppressing mesoscale clusterin"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.11.14.688546"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12642399"],"repository":["biostudies-literature"],"pubmed_title":["Nuclear-import receptors remodel the dilute phase to suppress phase transitions of RNA-binding proteins with prion-like domains."],"pmcid":["PMC12642399"],"funding_grant_id":["R01 AG077771","K99 GM152778","R01 NS121114","R35 GM138211"],"pubmed_authors":["Bugaj LJ","Mumford TR","Pappu RV","Shorter J","Shinn MK","Linsenmeier M","Liu V"],"additional_accession":[]},"is_claimable":false,"name":"Nuclear-import receptors remodel the dilute phase to suppress phase transitions of RNA-binding proteins with prion-like domains.","description":"RNA-binding proteins (RBPs) with prion-like domains, including FUS, hnRNPA1, and hnRNPA2, assemble into functional, metastable condensates that organize ribostasis, but can also transition into self-templating fibrils implicated in neurodegenerative proteinopathies such as amyotrophic lateral sclerosis (ALS). How nuclear-import receptors (NIRs) antagonize this pathological transition has remained unresolved. Here, we establish that NIRs regulate the phase behavior of prion-like cargos by remodeling the dilute phase. Quantitative analyses across length scales reveal that Karyopherin-β2 (Kapβ2) preferentially binds cargo in the dilute phase to lower the effective concentration of free RBPs thereby elevating the saturation concentration for phase separation and suppressing mesoscale clusterin","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-02T03:17:52.919Z","creation":"2026-06-02T03:09:02.449Z"},"accession":"S-EPMC12642399","cross_references":{"pubmed":["41292773"],"doi":["10.1101/2025.11.14.688546"]}}