{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cabaj M"],"funding":["NCATS NIH HHS","NIA NIH HHS","NINDS NIH HHS","NCI NIH HHS","NIGMS NIH HHS","NIH HHS"],"pagination":["116145"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12422362"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(8)"],"pubmed_abstract":["The protein α-synuclein, encoded by SNCA, accumulates in Parkinson's disease (PD) and other synucleinopathies for reasons that remain unclear. Here, we investigated whether SNCA is regulated in vivo by the RNA-binding protein PUM1. We establish that PUM1 binds to SNCA's 3' UTR in mouse and human cells. In induced neurons from patients with SNCA locus triplication, PUM1 mRNA levels are lower than in healthy controls, but increasing PUM1 normalizes both SNCA mRNA and α-synuclein protein levels, largely by suppressing the long 3' UTR SNCA isoform. In microfluidic chamber experiments, silencing PUM1 causes a redistribution of SNCA between the soma and axons. We also show that the previously described miR-7 regulation of SNCA mRNA requires PUM1. Lastly, we report finding several individuals wit"],"journal":["Cell reports"],"pubmed_title":["Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1."],"pmcid":["PMC12422362"],"funding_grant_id":["R01 NS036630","F31 NS113574","R01 NS125018","S10 OD016167","R35 GM145279","R56 NS036630","R01 CA251753","R01 NS109858","R01 NS128142","T32 GM007088","R01 NS119690","T32 NS064928","TL1 TR001875","T32 AG000222"],"pubmed_authors":["Cabaj M","Singh RK","Khurana V","Roque CG","Baldwin K","Gaertner ZA","Gennarino VA","Hengst U","Randolph LK","Raimo S","Feeney S","Yalamanchili HK","Rajasekaran S","de Prisco N","Brandt V","Awatramani R","Wang R","Chemiakine A","Harms MB","Wang X","Miles W","Pauers MM","Zhang C","Mazzara PG"],"additional_accession":[]},"is_claimable":false,"name":"Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1.","description":"The protein α-synuclein, encoded by SNCA, accumulates in Parkinson's disease (PD) and other synucleinopathies for reasons that remain unclear. Here, we investigated whether SNCA is regulated in vivo by the RNA-binding protein PUM1. We establish that PUM1 binds to SNCA's 3' UTR in mouse and human cells. In induced neurons from patients with SNCA locus triplication, PUM1 mRNA levels are lower than in healthy controls, but increasing PUM1 normalizes both SNCA mRNA and α-synuclein protein levels, largely by suppressing the long 3' UTR SNCA isoform. In microfluidic chamber experiments, silencing PUM1 causes a redistribution of SNCA between the soma and axons. We also show that the previously described miR-7 regulation of SNCA mRNA requires PUM1. Lastly, we report finding several individuals wit","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-06-02T20:28:20.054Z","creation":"2026-04-20T03:09:59.993Z"},"accession":"S-EPMC12422362","cross_references":{"pubmed":["40815569"],"doi":["10.1016/j.celrep.2025.116145"]}}