title: Strand-specific RNA-sequencing analysis of multiple system atrophy brain transcriptome.
abstract: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease. The major pathological hallmark of MSA is the accumulation of α-synuclein in oligodendrocytes. In contrast to Parkinson's disease no definitive familial etiology for MSA has been determined. Yet, there is a growing body of evidence that perturbation of transcriptional processes leads to MSA pathology. Here we present the results of the first ribosomal-depleted strand-specific RNA-sequencing profile of the MSA brain frontal cortex tissue. Among the 123 differentially expressed genes over 50% were categorized as putative long intervening non-coding RNAs (lincRNAs). Along with the dysregulation of the non-coding portion of the transcriptome, the expression of protein coding genes was also affected, including serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3), interleukin 1 receptor-like 1 (IL1RL1) and hemoglobin, beta (HBB). Also of interest was the alternative splicing of SNCA, along with the presence of an antisense transcript overlapping the 3' exon of SNCA. Moreover, we demonstrate widespread antisense transcription throughout the frontal cortex that is largely not affected by MSA-specific neurodegenerative process. MSA causes a large disruption of lincRNAs in the human brain along with protein coding genes related to iron metabolism and immune response regulation. Most of the lincRNAs specific for MSA were novel. Hence our study uncovers another level of complexity in transcriptional pathology of MSA.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: J D
authors.initials: JD
authors.lastname: Mills
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Ward
authors.affiliation: Neuroscience Research Australia, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: W S
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Neuroscience Research Australia, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: G M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: m.janitz@unsw.edu.au.
authors.forename: M
authors.initials: M
authors.lastname: Janitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000378:metabolism; D059467:Transcriptome; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: antisense RNA; human brain; long intervening non-coding RNAs; multiple system atrophy; strand-specific RNA-Seq