Apr 13, 2020

lncRNA Mediated Hijacking of T-cell Hypoxia Response Pathway by Mycobacterium Tuberculosis Predicts Latent to Active Progression in Humans

BioRxiv : the Preprint Server for Biology
J. MehraTavpritesh Sethi


Cytosolic functions of Long non-coding RNAs including mRNA translation masking and sponging are major regulators of biological pathways. Formation of T cell- bounded hypoxic granuloma is a host immune defense for containing infected Mtb-macrophages. Our study exploits the mechanistic pathway of Mtb-induced HIF1A silencing by the antisense lncRNA-HIF1A-AS2 in T cells. Computational analysis of in-vitro T-cell stimulation assays in progressors (n=119) versus latent (n=221) tuberculosis patients revealed the role of lncRNA mediated disruption of hypoxia adaptation pathways in progressors. We found 291 upregulated and 227 downregulated lncRNAs that were correlated at mRNA level with HIF1A and HILPDA which are major players in hypoxia response. We also report novel lncRNA-AC010655 (AC010655.4 and AC010655.2) in cis with HILPDA, both of which contain binding sites for the BARX2 transcription factor, thus indicating a mechanistic role. Detailed comparison of infection with antigenic stimulation showed a non-random enrichment of lncRNAs in the cytoplasmic fraction of the cell in progressors. The lack of this pattern in non-progressors indicates the hijacking of the lncRNA dynamics by Mtb. The in-vitro manifestation of this response in ...Continue Reading

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Mentioned in this Paper

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Entire Occipital Lobe

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