A novel extended form of alpha-synuclein 3′UTR in the human brain
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-018-0371-x |
| _version_ | 1818338751986794496 |
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| author | Goun Je Subhrangshu Guhathakurta Seung Pil Yun Han Seok Ko Yoon-Seong Kim |
| author_facet | Goun Je Subhrangshu Guhathakurta Seung Pil Yun Han Seok Ko Yoon-Seong Kim |
| author_sort | Goun Je |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T15:16:06Z |
| format | Article |
| id | doaj.art-45e556dc25b14adabe55777859e66419 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-13T15:16:06Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-45e556dc25b14adabe55777859e664192022-12-21T23:40:42ZengBMCMolecular Brain1756-66062018-05-011111910.1186/s13041-018-0371-xA novel extended form of alpha-synuclein 3′UTR in the human brainGoun Je0Subhrangshu Guhathakurta1Seung Pil Yun2Han Seok Ko3Yoon-Seong Kim4Burnett School of Biomedical Sciences, College of Medicine, University of Central FloridaBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of MedicineNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of MedicineBurnett School of Biomedical Sciences, College of Medicine, University of Central FloridaAbstract 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.http://link.springer.com/article/10.1186/s13041-018-0371-xParkinson’s diseaseAlpha-synuclein3′ untranslated region (3′UTR)mRNA |
| spellingShingle | Goun Je Subhrangshu Guhathakurta Seung Pil Yun Han Seok Ko Yoon-Seong Kim A novel extended form of alpha-synuclein 3′UTR in the human brain Molecular Brain Parkinson’s disease Alpha-synuclein 3′ untranslated region (3′UTR) mRNA |
| title | A novel extended form of alpha-synuclein 3′UTR in the human brain |
| title_full | A novel extended form of alpha-synuclein 3′UTR in the human brain |
| title_fullStr | A novel extended form of alpha-synuclein 3′UTR in the human brain |
| title_full_unstemmed | A novel extended form of alpha-synuclein 3′UTR in the human brain |
| title_short | A novel extended form of alpha-synuclein 3′UTR in the human brain |
| title_sort | novel extended form of alpha synuclein 3 utr in the human brain |
| topic | Parkinson’s disease Alpha-synuclein 3′ untranslated region (3′UTR) mRNA |
| url | http://link.springer.com/article/10.1186/s13041-018-0371-x |
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