PLX025348

GSE40710: aSyn polyA-RNAseq in PD and unaffected cortical brain samples

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

We sought to more precisely characterize the different alpha-synuclein (aSyn) 3UTR mRNA species in normal and PD human brain. High-throughput, whole-transcriptome sequencing of the 3UTR ends of polyadenylated mRNA transcripts (termed pA-RNAseq; see Methods) was performed on a cohort of 17 unaffected and 17 PD cerebral cortical tissue samples. This revealed 5 aSyn 3UTR isoforms, with lengths of 290, 480, 560, 1070 and 2520 nt. Of these, the 560 nt and 2520 nt forms were predominant. The existence and relative preponderance of these species was further confirmed by Northern Blot. We next hypothesized, that aSyn 3UTR selection might be altered in PD. Comparison of pA-RNAseq profiles from PD and unaffected cerebral cortex samples revealed an increase in the preponderance of the long 3UTR species (>560 nt) relative to shorter species (<560 nt). Such a relative increase in aSynL was confirmed by Quantitative real-time RT-PCR (rt-qPCR) and appeared specific for PD, as the increase was also observed by comparison to RNA from amyotrophic lateral sclerosis patient samples. We note that the modified aSyn 3UTR selection associated with PD patient tissue was detected in cerebral cortex tissue, which typically harbors pathological evidence of the disease process without frank cell loss; thus, this phenotype is unlikely to be a secondary consequence of neurodegeneration. SOURCE: Herve RHINN (hr2239@columbia.edu) - Columbia University