New directions for Ψ and m¹A decoding in mRNA: deciphering the stoichiometry and function

Molecular functions of m¹A modification in tRNA and mRNAs. (A) m¹A in tRNAs is modified by the TRMT6/TRMT61A complex and removed by ALKBH1/ALKBH3/FTO. The presence of m¹A58 in tRNA promotes translation. (B) The abundance of tRNA, tRNA-m¹A58, and tRNA-related effectors dynamically respond to various physiological and pathological processes, such as T cell activation. (C) tRNA-m¹A mediates the generation of tRFs (tRNA-derived fragments). (D) m¹A in the 5' UTR of nuclear-encoded mRNA enhances translation, while m¹A in the CDS region of mitochondrial-encoded mRNA inhibits translation. (E) YTH domain-containing proteins may also recognize m¹A in mRNA in vitro, and YTHDF2 mediates the decay of m¹A-containing mRNAs; however, further in vivo experiments are necessary to elucidate the direct or indirect interactions. (F) TDP-43 is a reader of m¹A. The presence of m¹A induces TDP-43 accumulation in stress granules (SGs) and disrupts the phase separation of TDP-43.