ABSTRACT
More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N-methyladenosine (mA), have been detected in mRNA, opening the window into the realm of epitranscriptomics. The mA modification is the most abundant modification in mRNA and non-coding RNA (ncRNA). At the molecular level, mA affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA (miRNA) maturation, playing essential roles in a range of cellular processes. The mA modification is regulated by three classes of proteins generally referred to as the "writer" (adenosine methyltransferase), "eraser" (mA demethylating enzyme), and "reader" (mA-binding protein). The mA modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology (YTH) family proteins, selectively bind to RNA and affect its fate in an mA-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the mA modification, and provide our insights into the mA-mediated gene regulation.
Subject(s)
Animals , Humans , Adenosine , Metabolism , Gene Expression Regulation , Methyltransferases , Chemistry , Metabolism , RNA, Messenger , Chemistry , Metabolism , RNA, Untranslated , Chemistry , Metabolism , RNA-Binding Proteins , Chemistry , Metabolism , TranscriptomeABSTRACT
More than 100 modifications have been found in RNA. Analogous to epigenetic DNA methylation, epitranscriptomic modifications can be written, read, and erased by a complex network of proteins. Apart from N-methyladenosine (mA), N-methyladenosine (mA) has been found as a reversible modification in tRNA and mRNA. mA occurs at positions 9, 14, and 58 of tRNA, with mA58 being critical for tRNA stability. Other than the hundreds of mA sites in mRNA and long non-coding RNA transcripts, transcriptome-wide mapping of mA also identifies >20 mA sites in mitochondrial genes. mA in the coding region of mitochondrial transcripts can inhibit the translation of the corresponding proteins. In this review, we summarize the current understanding of mA in mRNA and tRNA, covering high-throughput sequencing methods developed for mA methylome, mA-related enzymes (writers and erasers), as well as its functions in mRNA and tRNA.