We are glad to announce that Ramakrishna Mission Vivekananda Educational and Research Institute (RKMVERI) will be conducting a special colloquium on “The Happy, exciting and versatile life of Eukaryotic Messenger RNAs” on 21 March 2025, 12 Noon at Seminar Hall, Narendrapur Campus.

Speaker : Prof. Biswadip Das, Life Science & Biotechnology, JU
Co-ordinator: Prof. Abhijit Chakrabarti

Abstract

The life of a eukaryotic messenger RNA starts in the nucleus when a protein-coding gene is transcribed by RNA Polymerase II. The transcribing messages undergo three important modifications namely Capping at the 5′-terminus, splicing and polyadenylation at the 3′-terminus. These three processing events are accompanied by the association of numerous mRNA binding proteins and maturation factors. Concerted interplay and orchestrated interactions of these mRNA-binding proteins with the maturating messages eventually yield an export-competent mRNP that facilitates its nuclear export to cytoplasm, which is known as the mRNP biogenesis events. Once in the cytoplasm, the messenger RNA has several options, it can undergo at least one round of protein remodelling event, which can either promote its translation or sometimes repress its translation. Repression of translation typically leads to its intracellular transport from one sub-cellular territory, typically from nuclear periphery to other sub-cytoplasmic destinations. This highly regulated process is currently less understood but is promptly emerging which transformed our understanding about the life of the messenger RNAs. Once the mRNA reaches it specific destination then it undergoes another round of remodelling to undergo translation followed by its degradation in the dark crevices in the cytoplasm called P-bodies. Remarkably translation of many messenger RNAs are repressed in response to various kinds of stresses which is believed to be another kinds of regulation of the corresponding genes.

Notably, all the mRNP biogenesis events are error-prone and these errors associated in the eukaryotic mRNP biogenesis result in the formation of aberrant messages, which are linked to diverse human diseases, including cancers, autoimmune diseases, and neurodegenerative disorders. In a healthy cell, these faulty transcripts are promptly eliminated by the nuclear mRNA surveillance mechanism consisting of the nuclear RNA exosome and its three cofactors, TRAMP, CTEXT and NNS. This system plays a seminal role of safeguarding the cells/organisms from genetic catastrophe resulting from the detrimental effects of these faulty transcripts.

Interestingly, the recent research from our lab revealed that apart from the defective mRNAs, the decay system also targets/degrades a group (250 messages) of normal functional messages. Subsequent analysis unveiled that the degradation of these normal messages represents a novel means of gene regulation that is accomplished via reversible and dynamic mRNA decay. We demonstrated that the nuclear mRNA surveillance pathway finely tunes (i) the activity of Unfolded Protein Response (UPR) (ii) the cell’s adaptability to a low glucose environment, regulation of ribosome biogenesis during nutrient stress and telomere length under ethanol stress. These regulatory circuits employ the dynamic and preferential decay of two functional mRNAs mediated by the CTEXT/exosome. Interestingly, their nuclear decay further governs other cellular events such as nuclear mRNA export and nucleus-to-ER transport of mRNAs.