Abstract
RNA modifications are diverse post-transcriptional modifications that regulate RNA metabolism and gene expression. RNA modifications, and the writers, erasers, and readers that catalyze these modifications, serve as important signaling machineries in cellular stress responses and disease pathogenesis. In response to stress, RNA modifications are mobilized to activate or inhibit the signaling pathways that combat stresses, including oxidative stress, hypoxia, therapeutic stress, metabolic stress, heat shock, DNA damage, and ER stress. The role of RNA modifications in response to these cellular stressors is context- and cell-type-dependent. Due to their pervasive roles in cell biology, RNA modifications have been implicated in the pathogenesis of different diseases, including cancer, neurologic and developmental disorders and diseases, and metabolic diseases. In this review, we aim to summarize the roles of RNA modifications in molecular and cellular stress responses and diseases.
Highlights
RNA modifications are covalent chemical modifications of RNA molecules
These results suggest that loss of NSUN2 may be necessary to induce the cellular stress response [23]
Methylenetetrahydrofolate dehydrogenase 2 (MTHDF2), an enzyme that is important in one-carbon metabolism, is believed to regulate m6 A deposition on HIF-2α in renal cell carcinoma (RCC), which leads to increased HIF-2α translation, metabolic reprogramming, and tumor progression [65,66]
Summary
RNA modifications are covalent chemical modifications of RNA molecules. To date, over 100 chemical modifications of RNA species have been identified [1,2]. ‘readers’, which deposit, remove, and recognize RNA modifications, respectively (Figure 1A). These enzymes represent key elements in patterning the epitranscriptomic landscape. RNA modifications can occur on various RNA species including mRNA, tRNA, rRNA and other non-coding RNAs [3] (Figure 1B). Among these RNA species, transfer RNAs (tRNAs) contain the most RNA modifications [4]. The most abundant internal mRNA modification is N6-methyladenosine (m6A) [2]. M6A writers include mostmodifications abundant internal mRNA modification is N6 -methyladenosine (mmethyl transferase-like family members (METTL3, METTL14), Wilms.
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