Biology subjects

Kunar, R.

Publications and source records attributed to Kunar, R..

4 recordsLinked to original sources

bioRxiv2021

The Drosophila DCP2 is evolutionarily conserved in sequence and structure : insights from in silico studies of DmDCP2 orthologs and paralogs

The mRNA decapping proteins (DCPs) function to hydrolyze the 7-methylguanosine cap at the 5 end of mRNAs thereby, exposing the transcript for degradation by the exonuclease(s) and hence, play a pioneering role in the mRNA decay pathway. In Drosophila melanogaster, the mRNA decapping protein 2 (DCP2) is the only catalytically active mRNA decapping enzyme present. Despite its presence being reported across diverse species in the phylogenetic tree, a quantitative approach to the index of its conservation in terms of its sequence has not been reported so far. With structural and mechanistic insights being explored in the yeasts, the insect DCP2 has never been explored in the perspectives of structure and the indices of the conservation of its sequence and/or structure vis-a-vis topological facets. Being an evolutionarily conserved protein, the present endeavor aimed at deciphering the evolutionary relationship(s) and the pattern of conservation of the sequence of DCP2 across the phylogenetic tree as well as in sibling species of D. melanogaster through a semi-quantitative approach relying on multiple sequence alignment and analyses of percentage identity matrices. Since NUDIX proteins are functionally diverse, an attempt to identify the other NUDIX proteins (or, DCP2 paralogs) in D. melanogaster and compare and align their structural features with that of DCP2 through in silico approaches was endeavored in parallel. Our observations provide quantitative and structural bases for the observed evolutionary conservation of DCP2 across the diverse phyla and also, identify and reinforce the structural conservation of the NUDIX family in D. melanogaster.

bioinformatics↗

bioRxiv2020

A forward genetic approach to mapping a P-element second site mutation identifies DCP2 as a novel tumor suppressor in Drosophila melanogaster

The use of transposons to create mutants has been the cornerstone of Drosophila genetics in the past few decades. Transpositions often create second-site mutations, devoid of transposon insertion and thereby affect subsequent phenotype analyses. In a P-element mutagenesis screen, a second site mutant was discovered on chromosome 3 wherein the homozygous mutant individuals show the classic hallmarks of mutations in tumor suppressor genes including brain tumour and lethality, hence the mutant line was initially named as lethal (3) tumorous brain [l(3)tb]. Classical genetic approaches relying on meiotic recombination and subsequent complementation with chromosomal deletions and gene mutations mapped the mutation to CG6169, the mRNA decapping protein 2 (DCP2), on the left arm of the third chromosome (3L), and thus the mutation was renamed as DCP2l(3)tb. Fine mapping of the mutation further identified the presence of a Gypsy-LTR like sequence in the 5UTR coding region of DCP2, alongwith expansion of the adjacent upstream intergenic AT-rich sequence. The mutant phenotypes are rescued by Introduction of a functional copy of DCP2 in the mutant background, thereby establishing the causal role of the mutation and providing a genetic validation of the allelism. With the increasing repertoire of genes being associated with tumor biology this is the first instance that the mRNA decapping protein is being implicated in Drosophila tumourigenesis. Our findings therefore imply a plausible role for mRNA degradation pathway in tumorigenesis and identify DCP2 as a potential candidate for future explorations of cell cycle regulatory mechanisms.

genetics↗

bioRxiv2019

DCP2 plays multiple roles during Drosophila development - possible case of moonlighting?

mRNA decapping proteins (DCPs) are components of the P-bodies in the cell which are hubs of mRNAs targeted for decay and they provide the cell with a reversible pool of mRNAs in response to cellular demands. The Drosophila genome codes for two decapping proteins, DCP1 and DCP2 out of which DCP2 is the cognate decapping enzyme. The present endeavour explores the endogenous promoter firing, transcript and protein expression of DCP2 in Drosophila wherein, besides a ubiquitous expression across development, we identify active expression paradigm during dorsal closure and a plausible moonlighting expression in the Corazonin neurons of the larval brain. We also demonstrate that the ablation of DCP2 leads to embryonic lethality and defects in vital morphogenetic processes whereas a knockdown of DCP2 in the Corazonin neurons reduces the sensitivity to ethanol in adults, thereby ascribing novel regulatory roles to DCP2. Our findings unravel novel putative roles for DCP2 and identify it as a candidate for studies on the regulated interplay of essential molecules during early development in Drosophila, nay the living world.

cell biology↗

bioRxiv2019

Characterisation of l(3)tb as a novel tumour suppressor allele of DCP2 in Drosophila melanogaster

Mutants provide an excellent platform for the discovery and characterization of gene functions. The present communication is a pioneering treatise on a hitherto undescribed function of the gene coding for the mRNA decapping protein 2 (DCP2) in Drosophila melanogaster. DCP2, the gene coding for the mRNA decapping enzyme, has been studied in various model organisms in the light of maintenance of transcript abundance and stability but has never been implicated in tumourigenesis. Herein, we describe the mapping and characterization of a novel tumour suppressor allele of DCP2 (CG6169), which we named as lethal(3)tumorous brain [l(3)tb]. The homozygous mutant individuals show prolonged larval life, develop larval brain tumors and are lethal in the larval/pupal stages. The tumour is characterized by the presence of increased number of superficial neuroblasts, abnormal chromosomal condensation and causes overgrowth in the wing and the eye-antennal discs of the homozygous mutant larvae, all of which are rescued by the introduction of a functional copy of DCP2 in the mutant background, thereby establishing the causal role of the mutation and providing a genetic validation of the allelism. Our findings therefore ascribe a novel role of tumor suppression to DCP2 besides its cognate function of mRNA decapping and thereby identify it as a potential candidate for future research on tumorigenesis.

genetics↗