The Messenger RNA Surveillance in the Nucleus: Principle, Function and Links to Human Diseases

Productive expression of a gene involves the nuclear events of mRNP biogenesis consisting of transcription and multiple processing/modification events of the nascent mRNAs. Complexities involved in mRNP biogenesis leads to various errors in the resulting mRNPs, which potentially increases the possibility of production of abnormal, aggregation-prone and otherwise non-functional polypeptide chains. To prevent formation of such aberrant proteins, all eukaryotic cells evolve a wide array of mechanisms which constantly monitors the transcription and nuclear mRNP biogenesis events. Dubbed as the mRNA surveillance, these mechanisms principally require the activity of the eukaryotic RNA processing exosome and its cofactors, which promptly detect these faulty messages and selectively degrade them to prevent their undesired translation. Ranging from yeasts to humans, mRNA surveillance thus limits the accumulation of aberrant messages and safeguards the cells from their detrimental effects. Remarkably, recent research underscored that the mRNA surveillance machinery, the RNA exosome and its cofactor CTEXT together target and degrade a small of group of normal and functional messages and thereby control the cellular abundance of these mRNAs and thereby regulate a few crucial cellular processes including unfolded protein response and cellular response to nutrient stress. Remarkably, mutations in the components of the exosome and its cofactors lead to the dysfunction of the surveillance machinery, which are linked to a variety of human diseases and disorders. In this article, we examine the composition of the mRNA surveillance components, narrate their functions and finally illustrate the defects of surveillance machinery involved in various diseases with predicted mechanism of mutation induced disorders and finally project the frontline and forthcoming avenues of the future research.