a ramanathan

I started my research career in 2005 with Prof. Praba Senguttuvan, (Rtd.,), who is a pediatric nephrologist in Madras Medical College, Chennai. Her approaches in science taught me so much to be a successful researcher in the clinical aspect benefit of pediatric patients based on molecular studies/analysis. After my doctoral degree, I Joined as a postdoc in Prof. Nayef Jarrous' lab. He is an expert in Human Nuclear RNase P. He did his postdoc/collaboration research with Noble laureate Prof. Sydney Altman. I gathered numerous experiences in traditional/conventional biochemical analysis in his lab, particularly in radioactive experiments, RNA methodologies (non-coding RNA), mammalian cell culture, in-vitro transcription assay, RNase P assay, initiation complexes, etc. These experiences will expand further to advancement in biochemistry, particularly in the field of Human Nuclear RNase P and RNA polymerase III. My first project in his laboratory was "Pol III and its link to the innate immune condition." My contribution/finding is as follows: The innate immune system constitutes the front line of host defense against invading viruses. This system comprises several interrelated signal transduction pathways, implicating the viral DNA sensor RNA polymerase (Pol) III. However, this polymerase's genetic and functional links to innate immunity remain largely unknown. This study describes a homozygous missense mutation (D40H) in the POLR3E gene, coding for a protein subunit of Pol III, in a child patient with disseminated viral infections and Langerhans cell histiocytosis. This mutation is shown to be related to a deficiency in interferon induction and increased susceptibility of cells to infection by cytomegalovirus. DNA and RNA viruses and non-viral DNA induce the expression of POLR3E7. In this paper, we provide detailed evidence that the look of D40H mutant POLR3E leads to impaired transcription due to the assembly of malfunctioning initiation complexes of Pol III. My second project focuses on “tRNA and its splicing complex in human cells,” processing precursor tRNAs and splicing short introns from specific precursor tRNA isotypes. Splicing involves the release of the intron by an endonuclease and then ligating the flanking exons by a ligase. Existing data revealed that splicing of tRNA occurs in nuclei of human cells and Xenopus laevis oocytes, whereas it occurs on the surface of mitochondria in yeast. This discrepancy points to the stark evolutionary divergence in the molecular mechanisms controlling the biosynthesis of tRNA in eukaryotes. We have preliminary unpublished results, the molecular model that advocates the coexistence of tRNA processing activities in large initiation complexes assembled on human tRNA genes. Our mass spectrometry analysis confirms the presence of numerous tRNA enzyme components, including some specific proteins, in proficient initiation complexes, thus supporting the coupling of several enzymatic activities for tRNA biosynthesis in human cells. I plan to study/investigate the RNA Pol III (mainly transcribes the small non-coding RNAs) and its main function on natural and disease development of the human system progress.