Biology subjects

Mookherjee, D.

Publications and source records attributed to Mookherjee, D..

3 recordsLinked to original sources

bioRxiv2026

Non-translated mRNA levels determine P-body properties

Translational repression enables rapid adaptation to environmental changes. Under stress, translational repressed mRNA and mRNA decay factors accumulate in cytoplasmic processing bodies (PBs), implicated in mRNA storage and decay. PBs have been mostly studied under glucose starvation in yeast, yet, knowledge is limited under other stress conditions. Here, we identify a correlation between the level of translation attenuation and the number, brightness, fluidity and recruitment of PB core components. Stresses triggering strong translation attenuation caused the formation of few bright and more fluid PBs that recruit the decay factors en bloc. Conversely, weaker translation attenuation induced numerous, dim, more viscous PBs to which PB proteins were sequentially recruited. Importantly, increasing non-translated mRNA levels augmented the brightness of dim PBs and accelerated decay machinery recruitment. Finally, boosting RNA levels increased the size of Dhh1 helicase-containing droplets in vitro. Taken together, we propose a model in which the assembly pathway and biophysical properties of PBs are governed by non-translated mRNA abundance. TeaserBiophysical properties, protein composition and assembly pathways of processing bodies are dependent on available mRNA levels.

cell biology↗

bioRxiv2023

Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding ofproteins with alpha helical domains

Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we have quantified the expression of RPL39L in human pluripotent cells, cancer cell lines and tissue samples, and in mouse germ cells. We generated RPL39L knock-out mouse embryonic stem cell (mESC) lines and demonstrated that RPL39L impacts the dynamics of translation, to support the pluripotency and differentiation, spontaneous and along the germ cell lineage. Most differences in protein abundance between WT and RPL39L KO lines were explained by widespread proteasomal activity. By CryoEM analysis of purified RPL39 and RPL39L-containing ribosomes we found that, unlike RPL39, RPL39L has two distinct conformations in the exposed segment of the nascent peptide exit tunnel, creating a distinct hydrophobic patch that has been predicted to support the efficient co-translational folding of alpha helices. Our study shows that ribosomal protein paralogs provide switchable modular components that can tune translation to the protein production needs of individual cell types.

molecular biology↗

bioRxiv2019

Maximization of non-nitrogenous metabolite production in E. coli using population systems biology

The E. coli metabolome is an interconnected set of enzymes that has measurable kinetic parameters ascribed for the production of most of its metabolites. Flux Balance Analysis (FBA) or Ordinary Differential Equation (ODE) models are used to increase product yield using defined media. However, they either give a range (FBA) or exact amount (ODE) of metabolite yield which isnt true as the transcriptome diversity of individual cells isnt considered. We formulate the metabolic-behaviour of individual cells by using a POpulation SYstems-Biology ALgorithm (POSYBAL) which predicts multiple-gene knockouts for increasing industrially relevant metabolites. We validate this prediction for producing isobutanol (Heterogenous metabolite) and shikimate (Homogenous metabolite) where, the product-yield was increased by 40 times (~2000 ppm) and 42 times (~3000 ppm) respectively. Also, we introduce a nitrogen-swap in standard media to its low-nitrogen counterpart during post-growth phase to redistribute flux towards non-nitrogenous pathways for increasing overall product-yield. Further, our model shows growth-phase diversity in bacterial population even under normal glucose-uptake, portraying a real-world scenario of diverse and robust environment thus, making it evolutionarily favourable to threats such as anti-bacterial attack.

bioengineering↗