Non-m⁶A RNA modifications in haematological malignancies

Abstract

Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N⁶-methyladenosine (m⁶A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non-m⁶A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m⁶A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non-m⁶A RNA modifications. In this review, we mainly focus on the roles and implications of non-m⁶A RNA modifications, including N⁴-acetylcytidine, pseudouridylation, 5-methylcytosine, adenosine to inosine editing, 2′-O-methylation, N¹-methyladenosine and N⁷-methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non-m⁶A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non-m⁶A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non-m⁶A modifiers in blood cancer.

Keywords

epitranscriptomics / haematological malignancies / non-m ⁶A RNA modification

RIGHTS & PERMISSIONS

2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.