Research

Aneeshkumar A.G.

M. Sc.
Mahatma Gandhi University, Kottayam, Kerala

Ph. D.
Center for Cellular and Molecular Biology, Hyderabad

Postdoctoral Research
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 

Email
aneesh@nii.ac.in

 

Research Interest

Our interest is in elucidating the mechanistic details of the pathogenesis of the mutations in genes required for tRNA biogenesis. We focus on generating cerebral organoid experimental models for neurodevelopmental disorders caused by defective tRNA biogenesis. Moreover, we also investigate how intracellular pathogens manipulate host translational machinery by altering tRNA pools.

Group Members

Mr. Khem Singh Negi, Amber Lim

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 lead to immediate repression of general translation, while the translation of stress-related genes is 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 the regulation of gene expression during human development and infection. 

We use cerebral organoids generated from human embryonic stem cells to study the mechanisms of neurological disorders caused by mutations in tRNA biogenesis factors. Moreover, we use HIV as a model system to study the changes in host tRNA pool brought about by intracellular pathogens.

Selected Publications

  • Maraia RJ* and Arimbasseri AG*. (2017) Factors That Shape Eukaryotic tRNAomes: Processing, Modification and Anticodon–Codon Use. Biomolecules. 7(1). pii: E26. (PMID: 28282871). * corresponding author
  • 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
  • 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, 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)

Copyright © 2012 National Institute of Immunology. All Rights Reserved.