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In silico Analysis of Polymorphisms in microRNAs Deregulated in Alzheimer Disease

BACKGROUND: Alzheimer’s disease (AD) is a degenerative condition characterized by progressive cognitive impairment and dementia. Findings have revolutionized current knowledge of miRNA in the neurological conditions. Two regulatory mechanisms determine the level of mature miRNA expression; one is mi...

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Detalles Bibliográficos
Autores principales: Moraghebi, Mahta, Maleki, Reza, Ahmadi, Mohsen, Negahi, Ahmad Agha, Abbasi, Hossein, Mousavi, Pegah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024493/
https://www.ncbi.nlm.nih.gov/pubmed/33841080
http://dx.doi.org/10.3389/fnins.2021.631852
Descripción
Sumario:BACKGROUND: Alzheimer’s disease (AD) is a degenerative condition characterized by progressive cognitive impairment and dementia. Findings have revolutionized current knowledge of miRNA in the neurological conditions. Two regulatory mechanisms determine the level of mature miRNA expression; one is miRNA precursor processing, and the other is gene expression regulation by transcription factors. This study is allocated to the in-silico investigation of miRNA’s SNPs and their effect on other cell mechanisms. METHODS: We used databases which annotate the functional effect of SNPs on mRNA-miRNA and miRNA-RBP interaction. Also, we investigated SNPs which are located on the promoter or UTR region. RESULTS: miRNA SNP3.0 database indicated several SNPs in miR-339 and miR-34a in the upstream and downstream of pre-miRNA and mature miRNAs. While, for some miRNAs miR-124, and miR-125, no polymorphism was observed, and also miR-101 with ΔG -3.1 and mir-328 with ΔG 5.8 had the highest and lowest potencies to produce mature microRNA. SNP2TFBS web-server presented several SNPs which altered the Transcription Factor Binding Sites (TFBS) or generated novel TFBS in the promoter regions of related miRNA. At last, RBP-Var database provided a list of SNPs which alter miRNA-RBP interaction pattern and can also influence other miRNAs’ expression. DISCUSSION: The results indicated that SNPs microRNA affects both miRNA function and miRNA expression. Our study expands molecular insight into how SNPs in different parts of miRNA, including the regulatory (promoter), the precursor (pre-miRNA), functional regions (seed region of mature miRNA), and RBP-binding motifs, which theoretically may be correlated to the Alzheimer’s disease.