Cellular RNA adenosine

Cellular RNA adenosine refers to the adenosine nucleoside residues within various RNA species, including messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These residues are the primary sites for critical epitranscriptomic modifications, most notably N6-methyladenosine (m6A) and the conversion of adenosine to inosine (A-to-I editing) (Roundtree et al., 2017, Cell). m6A modification, regulated by writer enzymes like METTL3, plays a pivotal role in RNA stability, splicing, and translation efficiency, and its dysregulation is linked to various cancers (Yankova et al., 2021, Nature). A-to-I editing, catalyzed by Adenosine Deaminase Acting on RNA (ADAR) enzymes, can alter the genetic code at the RNA level, influencing protein function and diversity, particularly in the central nervous system (Nishikura, 2016, Nat Rev Mol Cell Biol). Therapeutically, these adenosines are targeted either by small molecules that inhibit the modifying enzymes or by site-specific antisense oligonucleotides designed to recruit editing machinery to specific sites to correct genetic mutations (Wave Life Sciences, 2023). While targeting cellular RNA adenosines offers a powerful mechanism for fine-tuning gene expression and correcting genetic errors, the ubiquity of these residues necessitates high specificity to avoid widespread off-target effects and systemic toxicity (ProQR Therapeutics, 2023).

Other names

RNA adenosine residuesAdenosine in RNAm6A sitesA-to-I editing sitesEpitranscriptomic adenosine

Modulation of RNA adenosine modifications, such as N6-methyladenosine (m6A) or adenosine-to-inosine (A-to-I) deamination, through enzyme inhibition or site-specific recruitment of editing machinery to alter RNA function, stability, or sequence.