Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Parkinson's Disease Model Overexpressing Human α-Synuclein and Influence of

Overview

Journal Front Neurosci

Date 2021 Mar 25

PMID 33762903

Citations 10

Authors

Linjing Shen

Changliang Wang

Liang Chen

Garry Wong

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) regulate gene expression and biological processes through specific genetic and epigenetic mechanisms. Recent studies have described a dysregulation of small non-coding RNAs in Parkinson's disease (PD) tissues but have been limited in scope. Here, we extend these studies by comparing the dysregulation of both miRNAs and piRNAs from transgenic () nematodes overexpressing pan-neuronally human α-synuclein wild-type (WT) (HASN OX) or mutant (HASN OX). We observed 32 miRNAs and 112 piRNAs dysregulated in HASN OX compared with WT. Genetic crosses of HASN OX PD animal models with null mutants, the ortholog of TDP-43, an RNA-binding protein aggregated in frontal temporal lobar degeneration, improved their behavioral deficits and changed the number of dysregulated miRNAs to 11 and piRNAs to none. Neuronal function-related genes , , , , and were predicted to be targeted by cel-miR-1018, cel-miR-355-5p ( and ), cel-miR-800-3p, and 21ur-1581 accordingly. This study provides a molecular landscape of small non-coding RNA dysregulation in an animal model that provides insight into the epigenetic changes, molecular processes, and interactions that occur during PD-associated neurodegenerative disorders.

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References

Gegg M, Schapira A . The role of glucocerebrosidase in Parkinson disease pathogenesis. FEBS J. 2018; 285(19):3591-3603. DOI: 10.1111/febs.14393. View

Vartiainen S, Aarnio V, Lakso M, Wong G . Increased lifespan in transgenic Caenorhabditis elegans overexpressing human alpha-synuclein. Exp Gerontol. 2006; 41(9):871-6. DOI: 10.1016/j.exger.2006.05.005. View

Pinar Karpinar D, Gajula Balija M, Kugler S, Opazo F, Rezaei-Ghaleh N, Wender N . Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson's disease models. EMBO J. 2009; 28(20):3256-68. PMC: 2771093. DOI: 10.1038/emboj.2009.257. View

Conway K, Lee S, Rochet J, Ding T, Williamson R, Lansbury Jr P . Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci U S A. 2000; 97(2):571-6. PMC: 15371. DOI: 10.1073/pnas.97.2.571. View

ORegan G, deSouza R, Balestrino R, Schapira A . Glucocerebrosidase Mutations in Parkinson Disease. J Parkinsons Dis. 2017; 7(3):411-422. DOI: 10.3233/JPD-171092. View

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N . The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25(16):2078-9. PMC: 2723002. DOI: 10.1093/bioinformatics/btp352. View

Nuzziello N, Ciaccia L, Liguori M . Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs' World. Cells. 2020; 9(1). PMC: 7017296. DOI: 10.3390/cells9010075. View

Shen L, Wang C, Chen L, Leung K, Lo E, Lakso M . TDP-1/TDP-43 potentiates human α-Synuclein (HASN) neurodegeneration in Caenorhabditis elegans. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10):165876. DOI: 10.1016/j.bbadis.2020.165876. View

Cuervo A, Stefanis L, Fredenburg R, Lansbury P, Sulzer D . Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 2004; 305(5688):1292-5. DOI: 10.1126/science.1101738. View

10.

Polymeropoulos M, Lavedan C, Leroy E, Ide S, Dehejia A, Dutra A . Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997; 276(5321):2045-7. DOI: 10.1126/science.276.5321.2045. View

11.

Yan Z, Hu H, Jiang X, Maierhofer V, Neb E, He L . Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res. 2011; 39(15):6596-607. PMC: 3159465. DOI: 10.1093/nar/gkr298. View

12.

Winner B, Jappelli R, Maji S, Desplats P, Boyer L, Aigner S . In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011; 108(10):4194-9. PMC: 3053976. DOI: 10.1073/pnas.1100976108. View

13.

Lee M, Stirling W, Xu Y, Xu X, Qui D, Mandir A . Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc Natl Acad Sci U S A. 2002; 99(13):8968-73. PMC: 124407. DOI: 10.1073/pnas.132197599. View

14.

Knight A, Yan X, Hamamichi S, Ajjuri R, Mazzulli J, Zhang M . The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson's models. Cell Metab. 2014; 20(1):145-57. PMC: 4097176. DOI: 10.1016/j.cmet.2014.04.017. View

15.

Tanaka M, Kim Y, Lee G, Junn E, Iwatsubo T, Mouradian M . Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. J Biol Chem. 2003; 279(6):4625-31. DOI: 10.1074/jbc.M310994200. View

16.

Cunningham F, Achuthan P, Akanni W, Allen J, Amode M, Armean I . Ensembl 2019. Nucleic Acids Res. 2018; 47(D1):D745-D751. PMC: 6323964. DOI: 10.1093/nar/gky1113. View

17.

Ruan Q, Harrington A, Caldwell K, Caldwell G, Standaert D . VPS41, a protein involved in lysosomal trafficking, is protective in Caenorhabditis elegans and mammalian cellular models of Parkinson's disease. Neurobiol Dis. 2009; 37(2):330-8. PMC: 2818321. DOI: 10.1016/j.nbd.2009.10.011. View

18.

Luk K, Kehm V, Carroll J, Zhang B, OBrien P, Trojanowski J . Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012; 338(6109):949-53. PMC: 3552321. DOI: 10.1126/science.1227157. View

19.

Schulze M, Sommer A, Plotz S, Farrell M, Winner B, Grosch J . Sporadic Parkinson's disease derived neuronal cells show disease-specific mRNA and small RNA signatures with abundant deregulation of piRNAs. Acta Neuropathol Commun. 2018; 6(1):58. PMC: 6038190. DOI: 10.1186/s40478-018-0561-x. View

20.

Recasens A, Dehay B, Bove J, Carballo-Carbajal I, Dovero S, Perez-Villalba A . Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol. 2013; 75(3):351-62. DOI: 10.1002/ana.24066. View