Abstract
The mRNA epitranscriptome imparts diversity to gene expression by installing chemical modifications. Advances in detection methods have identified chemical modifications in eukaryotic, bacterial, and viral messenger RNAs (mRNAs). The biological functions of modifications in mRNAs still remain to be understood. Chemical modifications are introduced in synthetic mRNAs meant for therapeutic applications to maximize expression from the synthetic mRNAs and to evade the host immune response. This overview provides a background of chemical modifications found in mRNAs, with an emphasis on pseudouridine and its known effects on the mRNA life cycle, its potential applications in synthetic mRNA, and the methods used to assess its effects on mRNA translation.
Highlights
The emerging field of epitranscriptomics has uncovered an additional layer of complexity in the regulation of gene expression that stems from the addition of RNA modifications posttranscriptionally
Among the modifications that have been identified in messenger RNAs (mRNAs), modifications of internal adenosines to N6methyladenosine (m6A) and pseudouridine (Ψ) occur most frequently
The findings indicate that modulation of an mRNA’s structure might be a critical checkpoint for the Ψ-mediated regulation of gene expression; additional studies to understand mRNA structural dynamics in vivo and their role in the process of pseudouridylation will help shed more light on this aspect
Summary
The emerging field of epitranscriptomics has uncovered an additional layer of complexity in the regulation of gene expression that stems from the addition of RNA modifications posttranscriptionally. More than 150 modifications have been identified in highly abundant noncoding RNAs RNAs (rRNAs), transfer RNAs (tRNAs), and small nuclear RNAs (snRNAs)) [1, 2] It was thought for a long time that posttranscriptional chemical modifications of RNA that affected the RNA’s biogenesis, function, and stability were limited to ncRNAs. the only modifications that were reported for proteincoding messenger RNAs (mRNAs) were those in the mRNA 50 cap (N7-methylguanosine (m7G)) and 30 poly(A) tail, internal inosine (I) modifications, and modifications of internal adenosines to N6methyladenosine (m6A) [1]. I summarize the current state of knowledge of mRNA modifications, highlighting their known effects on protein expression, and discuss the applications of mRNA modifications in the synthesis of functional mRNAs. I provide an overview of the methods used to assess the biological functions of mRNA modifications
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