Assistant Professor, Biochemistry and Molecular Genetics
- MSc, Life Sciences, Jawaharlal Nehru University
- PhD, Computational Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD)
- Postdoc, Genomics, University of Virginia
Biogenesis and Function of Transfer RNA-Related Fragments (tRFs)
My laboratory used computational methods to make novel biological discoveries about regulation of gene expression in cancers from genomic and transcriptomic data generated by consortia like The Cancer Genome Atlas (TCGA), Encyclopedia of DNA elements (ENCODE) etc. An unbiased approach of analyzing high-throughput small RNA sequencing data resulted in the discovery of a new class of small RNAs called transfer RNA fragments (tRFs). Ongoing projects in the lab examine how tRFs impact on gene expression and cancer.
TRFs are heterogeneous class of small RNAs, with the most abundant ones classified into groups: tRF-5 arising from 5 end of mature tRNA, tRF-3 from 3 end of mature tRNA, tRF-1 arising from 3 end of primary tRNA and tiRs (tRNA halves) that are generated by cleavage in the anticodon loop. While tRF1 is generated during tRNA maturation by RNase Z, not much is known of the factors responsible for the biogenesis of other tRFs viz. tRF5s, tRF3s and tiRs. Also, the biological function of a vast majority of the tRFs is unknown. Our analysis of the Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) of Argonaute (AGO) protein and cross-linking ligation and sequencing of hybrids (CLASH) data suggest that tRFs bind to Argonaute proteins (AGO) and base pair with target genes in a manner similar to miRNA. . By comparison with microRNAs, another family of small RNAs that bind to AGO proteins and base-pair with target genes, we hypothesize that tRFs will function as tumor suppressors or as oncogenes and be involved in cellular and pathological processes like apoptosis and neurodegeneration. We are also interested to understand the biogenesis and function of tRFs, specifically its gene-regulatory role in cancer. Finally to help achieve this goal and facilitate research on tRFs we created and maintain a publicly available database of tRFs called tRFdb (http://genome.bioch.virginia.edu/trfdb/index.php ) that lists the sequences of abundant tRFs in different species and potential target genes.