N⁶-Methyladenosine RNA Modification in Normal and Malignant Hematopoiesis

Over 170 nucleotide variants have been discovered in messenger RNAs (mRNAs) and non-coding RNAs so far. However, only a few of them, including N⁶-methyladenosine (m⁶A), 5-methylcytidine (m⁵C), and N¹-methyladenosine (m¹A), could be mapped in the transcriptome. These RNA modifications appear to be dynamically regulated, with writer, eraser, and reader proteins being identified for each modification. As a result, there is a growing interest in studying their biological impacts on normal bioprocesses and tumorigenesis over the past few years. As the most abundant internal modification in eukaryotic mRNAs, m⁶A plays a vital role in the post-transcriptional regulation of mRNA fate via regulating almost all aspects of mRNA metabolism, including RNA splicing, nuclear export, RNA stability, and translation. Studies on mRNA m⁶A modification serve as a great example for exploring other modifications on mRNA. In this chapter, we will review recent advances in the study of biological functions and regulation of mRNA modifications, specifically m⁶A, in both normal hematopoiesis and malignant hematopoiesis. We will also discuss the potential of targeting mRNA modifications as a treatment for hematopoietic disorders.