The emerging role of RNA modifications in the regulation of mRNA stability

Abstract

Many studies have highlighted the importance of the tight regulation of mRNA stability in the control of gene expression. mRNA stability largely depends on the mRNA nucleotide sequence, which affects the secondary and tertiary structures of the mRNAs, and the accessibility of various RNA-binding proteins to the mRNAs. Recent advances in high-throughput RNA-sequencing techniques have resulted in the elucidation of the important roles played by mRNA modifications and mRNA nucleotide sequences in regulating mRNA stability. To date, hundreds of different RNA modifications have been characterized. Among them, several RNA modifications, including N 6-methyladenosine (m 6 A), N 6 ,2′-O-dimethyladenosine (m 6 Am), 8-oxo-7,8-dihydroguanosine (8-oxoG), pseudouridine (Ψ), 5-methylcytidine (m 5 C), and N 4-acetylcytidine (ac 4 C), have been shown to regulate mRNA stability, consequently affecting diverse cellular and biological processes. In this review, we discuss our current understanding of the molecular mechanisms underlying the regulation of mammalian mRNA stability by various RNA modifications.

Similarity between mutation spectra in hypermutated genomes of rubella virus and in SARS-CoV-2 genomes accumulated during the COVID-19 pandemic

“…In support of the role of oxidative damage in SARS-CoV-2 genomes, is the increased prevalence of G to U substitutions which is consistent with the oxidation of guanines in the RNA plus-strand (Fig 2). G to U changes could be caused by an increased level of oxidative damage generating 8-oxoG in viral RNA within cells or during sequencing library preparation [47,48]. Frequent copying of 8-oxoG with A, would show up as G to U changes in the strand, where 8-oxoG was present.…”

On the Way to Understanding the Interplay between the RNA Structure and Functions in Cells: A Genome-Wide Perspective

“…As the RNA, in its life cycle, undergoes numerous post-transcriptional modifications, adding various chemical groups to their bases can significantly influence the RNA folding, stability, and interactions with cellular factors [94][95][96]. The aberration of RNA modification patterns has been associated with various diseases in human, such as cancerogenesis [97].…”

Single-nucleotide resolution of N6-adenine methylation sites in DNA and RNA by nitrite sequencing

“…3 The dynamics of m 6 A incorporation into RNA are regulated by "writers" (i.e., methyltransferases) and "erasers" (i.e., demethyltransferases), and can directly affect processes such as nuclear RNA export, splicing, and RNA stability. 4 Not surprisingly, the deregulation of these dynamics and resulting aberrant levels of m 6 A has been linked to obesity, immunoregulation, and cancer. 5 While 6mA has been widely known as a DNA modication in prokaryotes, its presence in eukaryotes has only been recently established, including in humans where it represents $0.051% of the genome.…”