MiRNA Expression and Interaction with the 3'UTR of FMR1 in FRAXopathy Pathogenesis

Overview

Journal Noncoding RNA Res

Date 2021 Jan 11

PMID 33426406

Citations 6

Authors

Alexander A Dolskiy

Andrey A Yarushkin

Irina V Grishchenko

Natalya A Lemskaya

Alexey V Pindyurin

Lidiya V Boldyreva

Vladimir O Pustylnyak

Dmitry V Yudkin

Affiliations

Soon will be listed here.

Abstract

FRAXopathies are caused by the expansion of the CGG repeat in the 5'UTR of the 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 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 gene activities were observed, allowing the identification of the relationships between dysregulation and miRNA activity. We studied the expression levels of eight miRNAs that target the gene. To prove the interaction of the studied miRNAs with , 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 gene. We evaluated changes in miRNA expression in response to alterations in gene activity in a model cell line as well as interactions with some miRNAs with the 3'UTR.

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