A novel extended form of alpha-synuclein 3′UTR in the human brain

Goun Je, Subhrangshu Guhathakurta, Seung Pil Yun, Hanseok Seok Ko, Yoon Seong Kim

Research output: Contribution to journalArticle

Abstract

Alpha-synuclein (α-SYN) is one of the key contributors in Parkinson's disease (PD) pathogenesis. Despite the fact that increased α-SYN levels are considered one of the key contributors in developing PD, the molecular mechanisms underlying the regulation of α-SYN still needs to be elucidated. Since the 3′ untranslated regions (3′UTRs) of messenger RNAs (mRNAs) have important roles in translation, localization, and stability of mRNAs through RNA binding proteins (RBPs) and microRNAs (miRNAs), it is important to identify the exact length of 3′UTRs of transcripts in order to understand the precise regulation of gene expression. Currently annotated human α-SYN mRNA has a relatively long 3′UTR (2529 nucleotides [nt]) with several isoforms. RNA-sequencing and epigenomics data have suggested, however, the possible existence of even longer transcripts which extend beyond the annotated α-SYN 3′UTR sequence. Here, we have discovered the novel extended form of α-SYN 3′UTR (3775 nt) in the substantia nigra of human postmortem brain samples, induced pluripotent stem cell (iPSC)-derived dopaminergic neurons, and other human neuronal cell lines. Interestingly, the longer variant reduced α-SYN translation. The extended α-SYN 3′UTR was significantly lower in iPSC-derived dopaminergic neurons from sporadic PD patients than controls. On the other hand, α-SYN protein levels were much higher in PD cases, showing the strong negative correlation with the extended 3′UTR. These suggest that dysregulation of the extended α-SYN 3′UTR might contribute to the pathogenesis of PD.

Original languageEnglish (US)
Article number29
JournalMolecular Brain
Volume11
Issue number1
DOIs
StatePublished - May 25 2018

Fingerprint

alpha-Synuclein
3' Untranslated Regions
Parkinson Disease
Brain
Induced Pluripotent Stem Cells
Dopaminergic Neurons
Messenger RNA
Nucleotides
RNA Sequence Analysis
RNA-Binding Proteins
Gene Expression Regulation
Substantia Nigra
MicroRNAs
Epigenomics
Protein Isoforms
Cell Line

Keywords

  • 3′ untranslated region (3′UTR)
  • Alpha-synuclein
  • mRNA
  • Parkinson's disease

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

A novel extended form of alpha-synuclein 3′UTR in the human brain. / Je, Goun; Guhathakurta, Subhrangshu; Yun, Seung Pil; Ko, Hanseok Seok; Kim, Yoon Seong.

In: Molecular Brain, Vol. 11, No. 1, 29, 25.05.2018.

Research output: Contribution to journalArticle

Je, Goun ; Guhathakurta, Subhrangshu ; Yun, Seung Pil ; Ko, Hanseok Seok ; Kim, Yoon Seong. / A novel extended form of alpha-synuclein 3′UTR in the human brain. In: Molecular Brain. 2018 ; Vol. 11, No. 1.
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