Saibal Chatterjee

Assistant Professor
Microbiology and Cell Biology
Research Areas: 
MicroRNA, turnover pathways, miRNAses,
Research Highlights: 

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate post-transcriptional expression of mRNAs, and collectively regulate diverse developmental and physiological processes. Although, initially thought to be 'super-stable' with half-lives on the order of days, 'microRNases' (miRNases) degrading mature animal miRNAs have recently been identified (eg. exoribonuclease 1/2, XRN-1/2). My research results suggested the presence of an additional layer of regulation of animal miRNA activity through miRNA turnover that might be important for bringing in rapid changes in miRNA expression profiles during developmental transitions and for the maintenance of steady-state concentrations of miRNAs. Accordingly, interference with these 'miRNases' results in upregulated miRNA activity, and that is consistent with an important regulatory function on miRNA activity. Intriguingly, recent reports are revealing that the stability of miRNAs can be regulated through differential turnover, where miRNA identity and tissue of expression playing decisive roles. I could also show that mature miRNA turnover and target-mediated mature miRNA protection (TMMP) together serve to maintain the robustness of the existing genetic makeup by acting subsequent to active miRISC formation, and thus I could advocate a post-loading proofreading mechanism that refines and diversifies miRISC programming. Further experimental results also suggested that TMMP paves evolutionary diversification of miRNAs from existing loci, by driving accumulation of previously unused passenger strands, once targets, and thus potential biological functions, have been acquired. In order to understand the miRNA turnover pathway better in future, biochemical, genetic, and cell biological analyses would be carried out to identify and characterize the different components of the miRNA turnover pathway in C. elegans, and establish their physiological significance. Both miRNA under-&-over-expression can cause developmental abnormalities and human diseases as deadly as cancer can result, but nothing about the pathway & the modus operandi of the miRNA turnover process in animals is known except the involvement of a few miRNases, let alone differential regulation of the pathway components following different biological and environmental stimuli-&-cues; leading to the different physiological states. Thus, understanding the mode of action of the 'miRNA turnover complexes' (miRNasomes), would be one key step to unravel miRNA turnover pathway, rather than the individual miRNases.

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