Research Topics
Department of Cell and Developmental Biology
Ph.D. (2000) Banaras Hindu University
Research Topics
Research Interests
More than 90% of the transcriptional output in mammalian genome consists of non-protein coding RNAs (ncRNAs). They can be broadly classified as small (some examples include microRNAs, 7SK RNA) and long (Xist RNA and RNAs present in mammalian imprinted loci) ncRNAs. The biological roles played by the regulatory (ncRNAs) are extremely diverse, ranging from their involvement in dosage compensation, imprinting, gene silencing and activation, intranuclear transport of factors and stress response. Recent data indicates the direct involvement of regulatory RNAs in various diseases including cancer and neurological disorders.
Interestingly, a sub-class of ncRNAs is retained in specific sub-nuclear compartments in the mammalian cell nucleus (Nuclear-retained regulatory RNAs; nrRNAs). Examples of nrRNAs include but are not limited to the class of polyadenylated RNA/s in interchromatin granule clusters (IGCs) or nuclear speckles, Xist and Tsix RNAs associated with X-chromosomes and small RNAs in Cajal bodies. The eukaryotic cell nucleus is the master regulator of gene expression and nuclear compartmentalization is a key feature that enables dynamic interplay between nuclear sub-domains and/or their constituents and the genome to foster the efficient progression of gene expression. Unlike most pre-mRNAs that get processed and transported to the cytoplasm, the nuclear-retained nrRNAs execute crucial roles within the nucleus. Identification and characterization of the complete compliment of nrRNAs in the mammalian genome, is essential towards understanding the myriad of ways in which nrRNAs regulate gene expression. The main focus of my laboratory is to characterize many of these mammalian nrRNAs and understand how they play important gene-regulatory roles.
By using a biochemical purification approach, we have identified several nrRNAs in the mammalian genome. One such regulatory RNA named CTN-RNA ( Cat2- Transcribed Nuclear-RNA) is converted from non-protein coding status to protein coding status in response to cellular stress such as a viral infection. Upon stress, CTN-RNA is post-transcriptionally processed and released from the nucleus, rapidly exported to the cytoplasm and translated into a protein, mCAT2 that is essential for cell survival. This post-trancriptional mechanism circumvents the time consuming and arduous process of synthesizing new mRNA, which in turn churns out a quick response during stress. The research efforts will focus on dissecting the cascade of events that regulate nuclear retention of CTN-RNA in normal cells and subsequently its post-trascriptional cleavage to eventually produce mCAT2 protein during cellular stress. This is the first example where RNA has been shown to undergo post-transcriptional cleavage. Characterizing the RNP complex that cleaves CTN-RNA and the pathway that triggers the cleavage would enable us to understand the molecular events that regulate this process. Since CAT2 protein is directly involved in the production of inducible Nitric Oxide, a tightly regulated cellular event, understanding how CTN-RNA controls the level of mCAT2 mRNA in the cell would have broad implications for biomedical research. The functional characterization of CTN-RNA and other nrRNAs have revealed unexpected ways these nrRNAs control various important biological processes. In general we will utilize a combination of molecular and cell biological tools to facilitate the understanding of the functional significance of nrRNAs in living cells (For the detailed lab projects, please see http://www.mcb.uiuc.edu/faculty/profile/1579).
Key Words Nucleus, non-coding RNA, Nuclear domains, RNA processing and transport, RNA-protein complex, RNA editing, Microscopy and Imaging analysis, Recombinant DNA, Gene Expression
Current Funding ICR