Vishal Kumar Sahu , Subhayan Sur , Sanjana Agarwal , Harishkumar Madhyastha , Amit Ranjan , Soumya Basu
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引用次数: 0
Abstract
MicroRNAs (miRNAs) belong to a short endogenous class of non-coding RNAs which have been well studied for their crucial role in regulating cellular homeostasis. Their role in the modulation of diverse biological pathways by interacting with cellular proteins, genes, and RNAs through cellular communication projects them as promising biomarkers and therapeutic targets. However, studying miRNA-protein interactions specific to disease in the extracellular or cell-free environments for drug discovery and biomarker establishment is challenging and resource-intensive due to their structural complexities. In this study, we present a computational approach to uncover patterns in miRNA-protein interactions in the cell-free milieu leveraging existing experimental data. We employed motif discovery tools, extracted motifs from 3D protein and miRNA structures, and conducted molecular docking analyses to identify and rank these interactions. This in silico-based approach reveals 204 and 2874 consensus sequences in miRNAs and proteins, respectively, within the interactome highlighting their potential roles in the cardiovascular diseases, neurological disorders, and cancers. The role of proteins like METTL3 and AGO2 and miRNAs such as hsa-miR-484 and hsa-miR-30 families, hsa-mir-126-5p has been discussed contextually. Additionally, we discovered simple sequence repeats in the consensus patterns having unexplored functional roles. Our observations provide new insights into the extracellular miRNA-protein interactions that may drive disease initiation and progression offering potential avenues for overcoming challenges like therapy relapse and drug inefficacy. The results of our analysis are available in the miRPin database (https://www.mirna.in/miRPin).
期刊介绍:
Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.