The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis

Abstract

Hematopoietic stem cells (HSCs) developing from mesoderm during embryogenesis are important for the blood circulatory system and immune system. Many factors such as genetic factors, chemical exposure, physical radiation, and viral infection, can lead to the dysfunction of HSCs. Hematological malignancies (involving leukemia, lymphoma, and myeloma) were diagnosed in more than 1.3 million people globally in 2021, taking up 7% of total newly-diagnosed cancer patients. Although many treatments like chemotherapy, bone marrow transplantation, and stem cell transplantation have been applied in clinical therapeutics, the average 5-year survival rate for leukemia, lymphoma, and myeloma is about 65%, 72%, and 54% respectively. Small non-coding RNAs play key roles in a variety of biological processes, including cell division and proliferation, immunological response and cell death. With the development of technologies in high-throughput sequencing and bioinformatic analysis, there is emerging research about modifications on small non-coding RNAs, as well as their functions in hematopoiesis and related diseases. In this study, we summarize the updated information of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis, which sheds lights into the future application of HSCs into the treatment of blood diseases.

Keywords: RNA modification; epigenetic; hematological malignances; hematopoietic stem cell; small non-coding RNAs.

FIGURE 1

HSC homeostasis is regulated by small non-coding RNAs: (A) miRNA processing, intercellular transmission, and intracellular regulation of mRNA expression. (B) snoRNA processing and its function on rRNA modification. (C) tRNA processing, intercellular communication, and translation-related intracellular action. (D) The origin of tsRNA and rsRNA, and their potential control at the DNA, RNA, and protein levels. (E) Different cleavage formations of circRNA and its effects on miRNA.

FIGURE 2

RNA modifications are involved in the regulation of hematopoiesis and hematological malignancies: (A) Reversible conversion of m6A modification and differential regulation function on mRNA and circRNA in hematologic cancers. (B) Pseudo is involved in the regulation of HSC by acting on rRNA to maintain telomere length or on tsRNA to modulate specific translation processes. (C) Abnormal 2′-O-Nm can cause mutations in other important genes and can also lead to severe morphological abnormalities and embryonic death.