Alpha-synuclein mRNA isoform formation and translation affected by polymorphism in the human SNCA 3'UTR.

ABSTRACT:

Background

Multiple variants in SNCA, encoding alpha-synuclein, a main component of Lewy bodies, are implicated in Parkinson's disease.

Methods

We searched for cis-acting SNCA variants using allelic mRNA ratios in human brain tissues. In a SNCA 3'UTR (2,520 bp) luciferase reporter gene assay, translation in SH-SY5Y cells in the presence of the rs17016074 G/A alleles was measured. To assess clinical impact, we queried neurocognitive genome-wide association studies.

Results

Allelic ratios deviated up to twofold, measured at a marker SNP in the middle of a long 3' untranslated region (3'UTR), but not at a marker at its start, suggesting regulation of 3'UTR processing. 3'UTR SNP rs17016074 G/A, minor allele frequency (MAF) <1% in Caucasians, 13% in Africans, strongly asso

SUBMITTER: Barrie ES 

PROVIDER: S-EPMC6081226 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature