Epitranscriptomics in myeloid malignancies.

Abstract

In eukaryotes, gene expression is highly orchestrated not only by genomic promoters and enhancers but also by covalent modifications added to either chromatin or RNAs. Traditionally, “epigenetics” refers to the chemical modifications that govern heritable changes in gene expression independent of the DNA sequence; “epitranscriptomics” indicates the covalent decorations in RNA, which plays a central role in posttranscriptional gene regulation. To date, >170 RNA chemical modifications have been characterized. Most of these modifications were originally identified in highly abundant noncoding RNA species, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and small nuclear RNA (snRNAs). Recently, the substantial advances in high-throughput sequencing and analytical chemistry have enabled the precise detection and characterization of chemical modifications in messenger RNA (mRNA). Indeed, a consid- erable number of mRNA decorations have been documented, including N 6 -methyladenosine (m 6 A); N 1 -methyladenosine (m 1 A); N 6 ,2 ʹ -O-dimethyladenosine (m 6 A m ); 3-methylcytidine (m 3 C); 5-methylcytidine (m 5 C); 5-hydroxymethylcytidine (hm 5 C); N 4 -acetylcytidine (ac 4 C); Adenosine-to-inosine (A-to-I) editing; pseudouridine ( Ψ ); N 7 -methylguanosine (m 7 G) and 2 ʹ -O-methylated nucleotides (