Strand-specific RNA-sequencing analysis of multiple system atrophy brain transcriptome. (13th May 2016)

• Record Type: Journal Article
• Authors: Mills, J.D.; Ward, M.; Kim, W.S.; Halliday, G.M.; Janitz, M.
• Is Part Of: Neuroscience. Volume 322(2016)
• Page Start: 234
• Page End: 250
• Publication Date: 2016-05-13
• Subjects: BACE1 beta-site APP-cleaving enzyme 1 -- BACE1-AS beta-site APP-cleaving enzyme 1 antisense -- BLAT BLAST-like alignment tool -- CAMK2A calcium/calmodulin-dependent protein kinase II alpha -- CNP 2, 3, -cyclic nucleotide 3, phosphodiesterase -- COQ2 Q2 4-hydroxybenzoate polyprenyltransferase -- CTGF connective tissue growth factor -- DAVID Database for Annotation, Visualization and Integrated Discovery -- DEGs differentially expressed genes -- DTNBP1 dystrobrevin binding protein 1 -- EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1 -- FEZ1 fasciculation and elongation protein zeta 1 -- fpkm fragments per kilobase of exon per million fragments mapped -- GCIs glial cytoplasmic inclusions -- GM gray matter -- GO gene ontology -- HBA1 hemoglobin alpha 1 -- HBA2 hemoglobin alpha 2 -- HBB hemoglobin beta -- IL1RL1 interleukin 1 receptor-like 1 -- ISH in situ hybridization -- KLC4-KLRK1 KLRC4-KLRK1 readthrough -- LINC00320 long intervening non-coding RNA 00320 -- lincRNAs long intervening non-coding RNAs -- LOC389831 uncharacterized LOC389831 -- LRRC3B leucine-rich repeat containing 3B -- LRRK2 leucine-rich repeat kinase 2 -- MALAT1 metastasis-associated lung adenocarcinoma transcript 1 -- MAP2 microtubule-associated protein 2 -- MBP myelin basic protein -- MFGE8 milk fat globule-EGF factor 8 protein -- miRNAs microRNAs -- MSA multiple system atrophy -- NDE1 NudE neurodevelopment protein -- NHPRTR Nonhuman Primate Reference Transcriptome -- NPY neuropeptide Y -- nts nucleotides -- NUP160 nuclear pore complex protein Nup 160 -- OLMALINC oligodendrocyte maturation-associated long intergenic non-coding RNA -- PD Parkinson's disease -- PMI post mortem interval -- poly(A)− polyadenylated negative -- poly(A)+ polyadenylated positive -- PRODH proline dehydrogenase (oxidase) 1 -- PTEN phosphatase and tensin homolog -- PTENpg1 phosphatase and tensin homolog pseudogene -- RGS4 regulator of G-protein signaling 4 -- RNA-Seq RNA-Sequencing -- RSS RNA secondary structure -- SERPINA1 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase antitrypsin) member 3 -- SFG superior frontal gyrus -- SLC1A2 solute carrier family 1 (glial high affinity glutamate transporter) member 2 -- SLC1A4 solute carrier family 1 (Glutamate/Neutral Amino Acid Transporter) member 4 -- SNCA α-synuclein -- SNCA-003 α-synuclein variant 003 -- SNCA-009 α-synuclein variant 009 -- SNCA-204 α-synuclein variant 204 -- SNCA-AS2 RP11-115D19.1-008 -- SNPs single nucleotide polymorphisms -- SOCS3 suppressor of cytokine signaling 3 -- SQSTM1 sequestosome 1 -- TTR transthyretin -- UCSC University of California, Santa Cruz -- VAT1L vesicle amine transport 1-like -- WM white matter; multiple system atrophy -- strand-specific RNA-Seq -- human brain -- long intervening non-coding RNAs -- antisense RNA; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.02.042
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: The first strand-specific RNA-sequencing study of multiple system atrophy. Evidence of widespread antisense transcription in the frontal cortex. Over 50% of the differentially expressed genes are putative lincRNAs. Metabolism and immune response genes are altered in the multiple system atrophy. 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.