TY - JOUR
T1 - Erythrocyte miRNA-92a-3p interactions with PfEMP1 as determinants of clinical malaria
AU - Prabhu, Sowmya R.
AU - Ware, Akshay Pramod
AU - Umakanth, Shashikiran
AU - Hande, Manjunath
AU - Mahabala, Chakrapani
AU - Saadi, Abdul Vahab
AU - Satyamoorthy, Kapaettu
N1 - Funding Information:
We gratefully acknowledge Dr. T.M.A. Pai Ph.D. fellowship, Manipal Academy of Higher Education (MAHE) and Indian Council of Medical Research (Ref. Id. 111/2022-ECD-II and BMI/11(10)/2022), Government of India, awarded to Sowmya R. Prabhu and Akshay Pramod Ware and MAHE Intramural Funding MAHE/DREG/PHD/IMF/2019. We thank MAHE, Manipal, Technology Information Forecasting and Assessment Council (TIFAC)-Core in Pharmacogenomics at MAHE, Manipal, Fund for Improvement of S&T Infrastructure (FIST), Department of Science and Technology, Government of India, Karnataka Fund, for Infrastructure Strengthening in Science and Technology (K-FIST), Government of Karnataka, and Builder, Department of Biotechnology, Government of India.
Funding Information:
We gratefully acknowledge Dr. T.M.A. Pai Ph.D. fellowship, Manipal Academy of Higher Education (MAHE) and Indian Council of Medical Research (Ref. Id. 111/2022-ECD-II and BMI/11(10)/2022), Government of India, awarded to Sowmya R. Prabhu and Akshay Pramod Ware and MAHE Intramural Funding MAHE/DREG/PHD/IMF/2019. We thank MAHE, Manipal, Technology Information Forecasting and Assessment Council (TIFAC)-Core in Pharmacogenomics at MAHE, Manipal, Fund for Improvement of S&T Infrastructure (FIST), Department of Science and Technology, Government of India, Karnataka Fund, for Infrastructure Strengthening in Science and Technology (K-FIST), Government of Karnataka, and Builder, Department of Biotechnology, Government of India.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - Based on the recently added high throughput analysis data on small noncoding RNAs in modulating disease pathophysiology of malaria, we performed an integrative computational analysis for exploring the role of human-host erythrocytic microRNAs (miRNAs) and their influence on parasite survival and host homeostasis. An in silico analysis was performed on transcriptomic datasets accessed from PlasmoDB and Gene Expression Omnibus (GEO) repositories analyzed using miRanda, miRTarBase, mirDIP, and miRDB to identify the candidate miRNAs that were further subjected to network analysis using MCODE and DAVID. This was followed by immune infiltration analysis and screening for RNA degradation mechanisms. Seven erythrocytic miRNAs, miR-451a, miR-92a-3p, miR-16-5p, miR-142-3p, miR-15b-5p, miR-19b-3p, and miR-223-3p showed favourable interactions with parasite genes expressed during blood stage infection. The miR-92a-3p that targeted the virulence gene PfEMP1 showed drastic reduction during infection. Performing pathway analysis for the human-host gene targets for the miRNA identified TOB1, TOB2, CNOT4, and XRN1 genes that are associated to RNA degradation processes, with the exoribonuclease XRN1, highly enriched in the malarial samples. On evaluating the role of exoribonucleases in miRNA degradation further, the pattern of Plasmodium falciparum_XRN1 showed increased levels during infection thus suggesting a defensive role for parasite survival. This study identifies miR-92a-3p, a member of C13orf25/ miR-17-92 cluster, as a novel miRNA inhibitor of the crucial parasite genes responsible for symptomatic malaria. Evidence for a plausible link to chromosome 13q31.3 loci controlling the epigenetic disease regulation is also suggested.
AB - Based on the recently added high throughput analysis data on small noncoding RNAs in modulating disease pathophysiology of malaria, we performed an integrative computational analysis for exploring the role of human-host erythrocytic microRNAs (miRNAs) and their influence on parasite survival and host homeostasis. An in silico analysis was performed on transcriptomic datasets accessed from PlasmoDB and Gene Expression Omnibus (GEO) repositories analyzed using miRanda, miRTarBase, mirDIP, and miRDB to identify the candidate miRNAs that were further subjected to network analysis using MCODE and DAVID. This was followed by immune infiltration analysis and screening for RNA degradation mechanisms. Seven erythrocytic miRNAs, miR-451a, miR-92a-3p, miR-16-5p, miR-142-3p, miR-15b-5p, miR-19b-3p, and miR-223-3p showed favourable interactions with parasite genes expressed during blood stage infection. The miR-92a-3p that targeted the virulence gene PfEMP1 showed drastic reduction during infection. Performing pathway analysis for the human-host gene targets for the miRNA identified TOB1, TOB2, CNOT4, and XRN1 genes that are associated to RNA degradation processes, with the exoribonuclease XRN1, highly enriched in the malarial samples. On evaluating the role of exoribonucleases in miRNA degradation further, the pattern of Plasmodium falciparum_XRN1 showed increased levels during infection thus suggesting a defensive role for parasite survival. This study identifies miR-92a-3p, a member of C13orf25/ miR-17-92 cluster, as a novel miRNA inhibitor of the crucial parasite genes responsible for symptomatic malaria. Evidence for a plausible link to chromosome 13q31.3 loci controlling the epigenetic disease regulation is also suggested.
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U2 - 10.1007/s10142-023-01028-w
DO - 10.1007/s10142-023-01028-w
M3 - Article
C2 - 36941394
AN - SCOPUS:85150751173
SN - 1438-793X
VL - 23
JO - Functional and Integrative Genomics
JF - Functional and Integrative Genomics
IS - 2
M1 - 93
ER -