SNCA long 3’UTR transcripts in patients with synucleinopathy

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Abstract

Introduction. Post-transcriptional and post-translational modifications of the alpha-synuclein protein are considered important links in the pathogenesis of Parkinson’s disease (PD) and multiple system atrophy (MSA). Regulation of mRNA stability and translational activity is primarily provided by the 3’untranslated region (3’UTR). The proportion of long 3’UTRs (3’UTR-L) is currently considered as a risk factor for PD.

Aim of the study. To assess the proportion of 3’UTR-L SNCA transcripts with in patients with PD and MSA, and the influence of single nucleotide polymorphisms (SNPs) in this gene on the 3’UTR-L/total SNCA mRNA ratio.

Material and methods. The concentration of SNCA and 3’UTR-L mRNAs was determined in blood leukocytes of 84 patients (Russian population) with PD, 50 patients with MSA, and 49 healthy volunteers, by quantitative RT-PCR. The proportion of 3’UTR-L was expressed as a percentage of the total SNCA mRNA. SNP was determined by Sanger sequencing.

Results. Overall, the proportion of 3’UTR-L did not differ significantly between the PD, MSA, and control groups: in PD, the median proportion of 3’UTR-L was 30.9%, in MSA – 28.5%, in the control group – 29.8%, p = 0.21. A decrease in the proportion of 3’UTR-L by 15–21% relative to the median value for the group was detected in PD patients in association with the «risk» genotype GG at rs356168, rs356165, and rs3756063; in the MSA patient group, a decrease of 13–15% was also noted in relationship with the GG genotype at rs356168, rs356165, and the CC genotype at rs2737029. An increase in the proportion of 3’UTR-L by 17% was noted only in the PD group for “protective” genotype AA at rs356168 and rs356165.

About the authors

Lyudmila S. Karan

Russian Center of Neurology and Neuroscience

Author for correspondence.
Email: lskaran@mail.ru
ORCID iD: 0000-0002-5927-460X

Researcher, Molecular Genetics Laboratory, 5th Neurological Department, Institute of Clinical and Preventive Neurology

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Natalia Yu. Abramycheva

Russian Center of Neurology and Neuroscience

Email: abramicheva@neurology.ru
ORCID iD: 0000-0001-9419-1159

Head of the Molecular Genetics Laboratory, 5th Neurological Department, Institute of Clinical and Preventive Neurology; Candidate of Biological Sciences

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Ivan V. Minaev

Russian Center of Neurology and Neuroscience

Email: minaev@neurology.ru
ORCID iD: 0000-0003-0728-8708

Neurologist of the 5th Neurological Department, Institute of Clinical and Preventive Neurology

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Tatyana A. Krutyakova

Lomonosov Moscow State University

Email: tanyapankratova_1997@mail.ru

2nd year master’s degree student at the Faculty of Biology

Russian Federation, Leninskie Gory, 1, Moscow, 119991

Anna O. Protopopova

Russian Center of Neurology and Neuroscience

Email: anna.pro@mail.ru
ORCID iD: 0000-0002-2798-0331

Junior Researcher, Molecular Genetics Laboratory, 5th Neurological Department, Institute of Clinical and Preventive Neurology

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Arina R. Protsenko

Russian Center of Neurology and Neuroscience

Email: proсenko.a.r@neurology.ru
ORCID iD: 0009-0000-5290-5045

Junior Researcher, Molecular Genetics Laboratory, 5th Neurological Department, Institute of Clinical and Preventive Neurology

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Irina A. Berdalina

Russian Center of Neurology and Neuroscience

Email: berdalina@neurology.ru
ORCID iD: 0009-0001-8707-180X

Statistician, Department of Higher Qualification Training, Institute of Medical Education and Professional Development

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Ekaterina Yu. Fedotova

Russian Center of Neurology and Neuroscience

Email: fedotova@neurology.ru
ORCID iD: 0000-0001-8070-7644

Head of the 5th Neurological Department, Institute of Clinical and Preventive Neurology; Doctor of Medical Sciences

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

Sergey N. Illarioshkin

Russian Center of Neurology and Neuroscience

Email: snillario@gmail.com
ORCID iD: 0000-0002-2704-6282

Director of the Brain Institute, Deputy Director; Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences

Russian Federation, Volokolamskoye shosse, 80, Moscow, 125367

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