TY - JOUR

T1 - miRNA expression and interaction with the 3′UTR of FMR1 in FRAXopathy pathogenesis

AU - Dolskiy, Alexander A.

AU - Yarushkin, Andrey A.

AU - Grishchenko, Irina V.

AU - Lemskaya, Natalya A.

AU - Pindyurin, Alexey V.

AU - Boldyreva, Lidiya V.

AU - Pustylnyak, Vladimir O.

AU - Yudkin, Dmitry V.

N1 - Funding Information: This work was supported by the Russian Science Foundation grant 16-14-10288 for plasmid construction and by the Russian Science Foundation grant 18-15-00099 for the rest of the study. Publisher Copyright: © 2020 [The Author/The Authors] Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - FRAXopathies are caused by the expansion of the CGG repeat in the 5′UTR of the FMR1 gene, which encodes the protein responsible for the synthesis of FMRP. This mutation leads to dramatic changes in FMRP expression at both the mRNA and protein levels. Evidence is emerging that changes in FMR1 mRNA expression can lead to the dysregulation of the miRNAs that target its 3′UTR. In the present work, B-lymphocyte cell lines obtained from patients with FRAXopathies were used, and a wide variety of FMR1 gene activities were observed, allowing the identification of the relationships between FMR1 dysregulation and miRNA activity. We studied the expression levels of eight miRNAs that target the FMR1 gene. To prove the interaction of the studied miRNAs with FMR1, a plasmid was constructed that possesses three primary structures: the miRNA gene, with expression driven by an inducible promoter; a constitutively expressed FusionRed reporter; and an eGFP reporter followed by the 3′UTR of the FMR1 gene. We evaluated changes in miRNA expression in response to alterations in FMR1 gene activity in a model cell line as well as interactions with some miRNAs with the FMR1 3′UTR.

AB - FRAXopathies are caused by the expansion of the CGG repeat in the 5′UTR of the FMR1 gene, which encodes the protein responsible for the synthesis of FMRP. This mutation leads to dramatic changes in FMRP expression at both the mRNA and protein levels. Evidence is emerging that changes in FMR1 mRNA expression can lead to the dysregulation of the miRNAs that target its 3′UTR. In the present work, B-lymphocyte cell lines obtained from patients with FRAXopathies were used, and a wide variety of FMR1 gene activities were observed, allowing the identification of the relationships between FMR1 dysregulation and miRNA activity. We studied the expression levels of eight miRNAs that target the FMR1 gene. To prove the interaction of the studied miRNAs with FMR1, a plasmid was constructed that possesses three primary structures: the miRNA gene, with expression driven by an inducible promoter; a constitutively expressed FusionRed reporter; and an eGFP reporter followed by the 3′UTR of the FMR1 gene. We evaluated changes in miRNA expression in response to alterations in FMR1 gene activity in a model cell line as well as interactions with some miRNAs with the FMR1 3′UTR.

KW - 3′UTR

KW - FMR1

KW - Fragile X associated tremor/ataxia syndrome

KW - Fragile X syndrome

KW - Fragile X-associated primary ovarian insufficiency

KW - miRNAs

UR - http://www.scopus.com/inward/record.url?scp=85097910633&partnerID=8YFLogxK

U2 - 10.1016/j.ncrna.2020.11.006

DO - 10.1016/j.ncrna.2020.11.006

M3 - Article

C2 - 33426406

AN - SCOPUS:85097910633

VL - 6

SP - 1

EP - 7

JO - Non-coding RNA Research

JF - Non-coding RNA Research

SN - 2468-0540

IS - 1

ER -