1996-2001 : Ph.D. (Molecular Biology) National Institute of Immunology, J.N.U. Campus New Delhi 110 067, INDIA
Thesis Title : Structure-function studies of Engineered N-terminal α1 helix of Heat labileenterotoxin chain B in Escherichia coli and Vibrio cholerae
1994-1996 : M. Sc. (Biochemistry)
Department of Biochemistry, Nagpur University, Nagpur, Maharashtra, INDIA
1991-1994 : B. Sc. (Microbiology, Biochemistry, Chemistry)
Nagpur University, Nagpur, Maharashtra, INDIA
Molecular Biology of Protein Biosynthesis
NIH Fellows Award for Research Excellence(NIH-FARE) for years 2005 and 2006.
The fundamental difference between prokaryotic and eukaryotic translation initiation is that the former uses Shine-Dalgarno (SD) sequence on the mRNA to recruit small ribosome subunit and locate AUG codon or rarely GUC, CUC or UUG codon as a translation start site, while the latter uses eIF4F complex to bind mRNA and locate AUG codon or rarely CUG, UUG or GUC as a start codon by 5` to 3` scanning mechanism. Some of the examples listed below shows the involvement of non-AUG codon as a translation start signal.
In Saccharomyces cerevisiae, GRS1 encodes two isoforms of Glycyl-tRNA synthetases, one initiates from upstream in-frame UUG codon (encoding signal sequence for mitochondrial import) while the regular cytoplasmic version initiates from downstream AUG codon. For the synthesis of Alanine t-RNA synthetase (ALA1) protein a consecutive ACG ACG codon are utilized as an alternate translation start site. It has been reported recently that MHC class-I molecule can load antigenic precursor which is synthesized by using CUG as an initiation codon recognized by leucine tRNA and non-conventional eIF2A translation initiation factor. A genome wide ribosomal profiling analysis of vivo translation study reported that translation initiation from upstream non-AUG codon is widespread in S. cerevisiae under starvation condition. However, the importance and the basic mechanism for these initiations are still unclear. A number of yeast mutants have been identified that are able to initiate at the non-AUG codons. These mutants were designated as Sui (Suppressor of initiation) phenotypes. Sui- phenotypes are novel mutations that causes break down of AUG codon selection fidelity. Thus, Sui- mutants provide an important tool to understand the molecular mechanism of non-AUG codon selection.
The focus of our lab is to understand the molecular mechanism of non-canonical translation initiation processes in Saccharomyces cerevisiae using molecular genetic techniques.
The key questions are as follows:
Currently, There are two main projects running in our lab.
Pankaj V. Alone
National Institute of Science Education and Research
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