m6A mRNA methylation: A pleiotropic regulator of cancer.

In recent days, RNA modifications are gaining the interest of biologist worldwide. Till date, a total of 171 RNA modifications has been reported, and the number may increase with advancing technologies. The mRNA undergoes modifications like m5M, hm5C, m1A, m6A and pseudouridine, collectively called as epitranscriptomic alterations, each of them has their functional significance. m6A modification is the most common one which occurs at the motif of RRm6AACH in mRNA. The altered profiles of these epitranscriptomic changes are reported in multiple cancers. The present review discusses the dynamic nature of functional enzymes called methyltransferase (writer), demethylase (erasers) and m6A binding proteins (readers) and importance of the balance between these proteins for the homeostasis of our body functions like metabolism, circadian rhythm, immune response, viral replications, embryogenesis and cancer development. Nevertheless, the main focus has been on cancer development and progression. The understanding of such differential modifications are at infancy and may provide bring about a paradigm shift in our understanding of cancer for management and treatment.

SETD2 as a regulator of N6-methyladenosine RNA methylation and modifiers in cancer.

Cancer is an unpleasant, painful disease. It is one of the most devastating diseases worldwide diminishing many lives. Many genetic and epigenetic changes occur before cancer develops. Mutation in SETD2 gene is one such example. RNA splicing, DNA damage repair, DNA methylation and histone methylation are some of the biological processes mediated by SETD2. SETD2 (histone H3 lysine 36 methyltransferase) is a frequently mutated gene in different types of cancer. Loss of SETD2 is associated with worse prognosis and aggressive phenotypes. Histone modification is one of the epigenetic regulation having a significant effect on gene regulation. N6-methyladenosine (m6A) mRNA modification is a well-known posttranscriptional modification playing a pivotal role in many normal and pathological processes affecting RNA metabolism. SETD2 catalyses H3K36 trimethylation and in turn H3K36me3 guides the deposition of m6A on nascent RNA transcripts. Finally, this review summarizes the deep understanding of the role of SETD2 in RNA methylation/modification and how SETD2 mutation contributes to tumour development.