Mahatma Gandhi University, Kottayam, Kerala
Center for Cellular and Molecular Biology, Hyderabad
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD USA
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC USA
We focus on understanding the role of small non-coding RNAs in cell physiology with particular interest in the post transcriptional modifications of tRNAs. A combination of genetics and biochemistry based approaches is used to understand the regulation of tRNA activity and translation during development and environmental stress. Fission yeast S. pombe and embryonic stem cells are the experimental systems we use.
Mr. Khem Singh Negi
Summary of Research
tRNAs are among the most ancient non-coding RNA molecules that made the life as we know it possible. Their evolution as an adapter that links highly different chemistries of nucleic acids and proteins was probably one of the most important innovations during evolution. This important and essential function of tRNAs placed significant evolutionary restraints on the structure and sequence of tRNAs. But, tRNAs are no longer considered just as adapters in protein synthesis; they are appreciated as a major component of the mechanisms that regulate translation.
Translation is a major hub for regulation of gene expression. For example, almost all kinds of stress leads to immediate repression of general translation, while the translation of stress related genes are upregulated. Altering tRNA decoding activity by regulating the post transcriptional modifications is a mechanism to fine tune translation dynamics under different growth conditions. We address the role tRNAs and different tRNA modifications in regulation of gene expression during environmental stress and human development.
We use S. pombe genetics to probe novel concepts in the regulation of translation by tRNA modifications. S. pombe is a particularly useful system to study tRNA modifications as the tRNA modification machinery in S. pombe appears to be more similar to metazoans than the popular model organism S. cerevisiae. Moreover, genetic manipulation of S. pombe is easier than that of the metazoan cells. A parallel approach to understand the function of tRNA modifications in human development utilizes cerebral organoids developed from pluripotent stem cells. Cerebral organoids are 3-dimensional neuronal structures developed from pluripotent stem cells and serve as an experimental system to study gene expression changes during development.
- Arimbasseri AG, Iben JR, Wei F, Rijal K, Tomizawa K, Hafner M and Maraia RJ. (2016) Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer require N6-isopentenylation of A37. RNA. 22(9): 1400-1410 (PMID: 27354703)
- Arimbasseri AG and Maraia RJ. (2016) RNA Polymerase III advances: Structural and tRNA functional views. Trends in Biochemical Sciences. 41(6): 546-559 (PMID: 27068803)
- Arimbasseri AG, Blewett NH, Iben J, Lamichhane TN, Cherkasova V, Hafner M, Maraia RJ. (2015) RNA polymerase III output is functionally linked to tRNA dimethyl-G26 modification. PLoS Genetics. 11(12): e1005671. (PMID: 26720005). a. Accompanying Perspective by M. Boguta, PLoS Genetics 11(12): e1005743
- Lamichhane TN, Arimbasseri AG, Iben JR, Wei F, Tomizawa K and Maraia RJ. (2015) Lack of tRNA-i6A37 modification causes mitochondrial-like metabolic phenotype in S. pombe by limiting activity of cytosolic tRNATyr. RNA.22(4): 583-596 (PMID: 26857223)
- Arimbasseri AG and Maraia RJ. (2015) A high density of cis-information terminates RNA Polymerase III on a two-rail track. RNA Biology. 13(2): 166-171. (PMID: 26636900).
- Arimbasseri AG and Maraia RJ. (2015) Mechanism of transcription termination by RNA polymerase III utilizes a nontemplate-strand sequence-specific signal element. Molecular Cell. 58(6): 1124-1132. (PMID: 25959395) a. Accompanying Preview by Artsimovitch & Belogurov, Molecular Cell 58(6): 974-976.
- Arimbasseri AG and Maraia RJ (2015) Biochemical analysis of transcription termination by RNA polymerase III from yeast Saccharomyces cerevisiae. Methods in Molecular Biology. 1276:185-98.(PMID: 25665564)
- Arimbasseri AG, Kassavetis GA and Maraia RJ. (2014) Comment on Mechanism of eukaryotic RNA polymerase III transcription termination. Science. 345(6196): 524. (PMID: 25082694)
- Rijal K, Maraia RJ and Arimbasseri AG* (2015) A methods review on use of nonsense suppression to study 3' end formation and other aspects of tRNA biogenesis. Gene 556(1): 35-50. (PMID: 25447915) (* Corresponding author)
- Arimbasseri AG and Maraia RJ (2013) Distinguishing core and holoenzyme mechanisms of transcription termination by RNA polymerase III. Mol Cell Biol. 33(8): 1571-1581 (PMID: 23401852)
- Arimbasseri AG, Rijal K and Maraia RJ. (2013) Comparative overview of the RNA polymerase III & II transcription cycles, with focus on pol III termination and reinitiation. Transcription 4(6) (PMID: 24374331)
- Arimbasseri AG, Rijal K and Maraia RJ. (2013) Transcription termination by eukaryotic RNA polymerase III. Biochim Biophys Acta. 1829(3-4): 318-330 (PMID: 23099421)
- Maraia RJ, Arimbasseri AG (2013) It's Sno'ing on Pol III at nuclear pores. Genome Biol. 14(10):137. (PMID: 24176203)
- Iben JR, Mazeika JK, Hasson S, Rijal K, Arimbasseri AG, Russo AN, and Maraia RJ. (2011). Point mutations in the Rpb9-homologous domain of Rpc11 that impair transcription termination by RNA polymerase III. Nucleic Acids Res. 39, 6100-6113 (PMID: 21450810)
- Arimbasseri AG and Bhargava P. (2008) Chromatin Structure and Expression of a Gene Transcribed by RNA Polymerase III Are Independent of H2A.Z Deposition. Mol Cell Biol. 28(8): 2598-2607 (PMID: 18268003)