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Various RNA-binding proteins and their conditional networks explain miRNA biogenesis and help to reveal the potential SARS-CoV-2 host miRNAome system

Upendra Kumar Pradhan, Prince Anand, Nitesh Kumar Sharma, Prakash Kumar, Ashwani Kumar, Rajesh Pandey, Yogendra Padwad, Ravi Shankar
doi: https://doi.org/10.1101/2020.06.18.156851
Upendra Kumar Pradhan
1Studio of Computational Biology & Bioinformatics, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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Prince Anand
2Pharmacology and Toxicology Lab, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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Nitesh Kumar Sharma
1Studio of Computational Biology & Bioinformatics, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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Prakash Kumar
1Studio of Computational Biology & Bioinformatics, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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Ashwani Kumar
1Studio of Computational Biology & Bioinformatics, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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Rajesh Pandey
4Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, 110007, India
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Yogendra Padwad
2Pharmacology and Toxicology Lab, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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Ravi Shankar
1Studio of Computational Biology & Bioinformatics, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur (HP), 176061, India
3Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT) Palampur (HP), 176061, India
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  • For correspondence: ravish@ihbt.res.in
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Abstract

Background In-spite of ubiquitous expression of DROSA/DICER, miRNA formation and maturation are highly spatiotemporal implying involvement of other factors in their biogenesis. Several key studies have elucidated functions of few other RNA-binding proteins (RBPs) in miRNAs biogenesis, making it necessary to look miRNA biogenesis models with fresh approach.

Results A comprehensive study of >25TB of high-throughput data revealed that various combinations of RBPs and their networks determine the miRNA pool, regardless of DROSHA/DICER. The discovered RBP and miRNA associations displayed strong functional alliances. An RBP, AAR2, was found highly associated with miRNAs biogenesis, which was experimentally validated. The RBPs combinations and networks were tested successfully across a large number of experimentally validated data and cell lines for the observed associations. The RBP networks were finally modeled into a XGBoosting-regression based tool to identify miRNA profiles without any need of doing miRNA-seq, which scored a reliable average accuracy of 91% on test sets. It was further tested across >400 independent experimental samples and scored consistently high accuracy. This tool was applied to reveal the miRNAome of Covid19 patients about which almost negligible information exists. A significant number of Covid19 specific miRNA targets were involved in IFN-gamma, Insulin/IGF/P3K/AKT, and Ub-proteasome systems, found in cross-talk with each other and down-regulated heavily, holding promise as strong candidates for therapeutic solution. A large number of them belonged to zinc-finger family.

Conclusion There are several RBPs and their networks responsible for miRNA biogenesis, regardless of DROSHA/DICER. Modeling them successfully can reveal miRNAomes with deep reaching impact.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 22, 2020.
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Various RNA-binding proteins and their conditional networks explain miRNA biogenesis and help to reveal the potential SARS-CoV-2 host miRNAome system
Upendra Kumar Pradhan, Prince Anand, Nitesh Kumar Sharma, Prakash Kumar, Ashwani Kumar, Rajesh Pandey, Yogendra Padwad, Ravi Shankar
bioRxiv 2020.06.18.156851; doi: https://doi.org/10.1101/2020.06.18.156851
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Various RNA-binding proteins and their conditional networks explain miRNA biogenesis and help to reveal the potential SARS-CoV-2 host miRNAome system
Upendra Kumar Pradhan, Prince Anand, Nitesh Kumar Sharma, Prakash Kumar, Ashwani Kumar, Rajesh Pandey, Yogendra Padwad, Ravi Shankar
bioRxiv 2020.06.18.156851; doi: https://doi.org/10.1101/2020.06.18.156851

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