Deciphering Epitranscriptome: Modification of mRNA Bases Provides a New Perspective for Post-transcriptional Regulation of Gene Expression

Abstract

Gene regulation depends on dynamic and reversibly modifiable biological and chemical information in the epigenome/epitranscriptome. Accumulating evidence suggests that messenger RNAs (mRNAs) are generated in flashing bursts in the cells in a precisely regulated manner. However, the different aspects of the underlying mechanisms are not fully understood. Cellular RNAs are post-transcriptionally modified at the base level, which alters the metabolism of mRNA. The current understanding of epitranscriptome in the animal system is far ahead of that in plants. The accumulating evidence indicates that the epitranscriptomic changes play vital roles in developmental processes and stress responses. Besides being non-genetically encoded, they can be of reversible nature and involved in fine-tuning the expression of gene. However, different aspects of base modifications in mRNAs are far from adequate to assign the molecular basis/functions to the epitranscriptomic changes. Advances in the chemogenetic RNA-labeling and high-throughput next-generation sequencing techniques are enabling functional analysis of the epitranscriptomic modifications to reveal their roles in mRNA biology. Mapping of the common mRNA modifications, including N6-methyladenosine (m6A), and 5-methylcytidine (m5C), have enabled the identification of other types of modifications, such as N1-methyladenosine. Methylation of bases in a transcript dynamically regulates the processing, cellular export, translation, and stability of the mRNA; thereby influence the important biological and physiological processes. Here, we summarize the findings in the field of mRNA base modifications with special emphasis on m6A, m5C, and their roles in growth, development, and stress tolerance, which provide a new perspective for the regulation of gene expression through post-transcriptional modification. This review also addresses some of the scientific and technical issues in epitranscriptomic study, put forward the viewpoints to resolve the issues, and discusses the future perspectives of the research in this area.

Interaction Between Macro‐ and Micro-Nutrients in Plants

“…Moreover, the role of miRNAs as a potential regulator of the cross-talks between the nutrient homeostasis is also being deciphered ( Hsieh et al, 2009 ; Pant et al, 2009 ; Liang et al, 2015 ; Pueyo et al, 2021 ). The involvement of epigenetic and epitranscriptomic marks ( Wang et al, 2016 ; Kumar et al, 2018 ; Kumar and Mohapatra, 2021 ) in regulating nutrient interactions is yet to be explored. The need of the day is to conduct more extensive, multi-level interaction studies with a system biology approach, and to decipher the integrative gene-networks to better manage the nutrient deficiencies in crop plants, towards maximizing the yield and quality of the produce ( Kumar, 2018 ).…”

Dynamics of DNA Methylation and Its Functions in Plant Growth and Development

“…However, the exact mechanisms of regulating gene expression by DNA methylation in the promoter region and the gene-body are not yet clear. Since, only 5% of the genes in Arabidopsis are methylated in the promoter region, which indicates that DNA methylation is not the sole epigenetic regulatory mechanism for controlling the expression of genes (Zhang et al, 2018a;Kumar and Mohapatra, 2021). Crop plants with a large genome size possess a higher number of TEs, and many of them are closer to genes affecting their expression.…”

“…While DNA viruses are targeted through TGS to restrict their proliferation (Rodríguez-Negrete et al, 2009), RNA viruses are not influenced by DNA methylation. However, methylation of RNA bases, e.g., N 6 -methyladenosine (m 6 A; Gokhale et al, 2016;Kumar and Mohapatra, 2021), controls viral replication as well as the interaction between virus and host (Brocard et al, 2017;Dang et al, 2019). Hundreds of DMRs were identified to be influenced by a viral infection in tobacco, several of which were reported to be associated with gene expression to regulate host antiviral defense (Wang et al, 2018b).…”

NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation in vitro

“…Accumulating evidence have shown that epigenetic modifications of mRNA are crucial for RNA biology (Yue et al, 2015;Kumar and Mohapatra, 2021), including translation (Meyer et al, 2015;Huang et al, 2018), splicing (Xiao et al, 2016), transport (Roundtree et al, 2017) and degradation (Wang et al, 2014;Huang et al, 2018). Two m6A readers, YTHDF2 and YTHDC1, have been reported to play an important role in mouse oocyte maturation.…”