snoRNAs in hematopoiesis and blood malignancies: A comprehensive review

Abstract

Small nucleolar RNAs (snoRNAs) are noncoding RNA molecules of highly variable size, usually ranging from 60 to 150 nucleotides. They are classified into H/ACA box snoRNAs, C/D box snoRNAs, and scaRNAs. Their functional profile includes biogenesis of ribosomes, processing of rRNAs, 2′‐O‐methylation and pseudouridylation of RNAs, alternative splicing and processing of mRNAs and the generation of small RNA molecules like miRNA. The snoRNAs have been observed to have an important role in hematopoiesis and malignant hematopoietic conditions including leukemia, lymphoma, and multiple myeloma. Blood malignancies arise in immune system cells or the bone marrow due to chromosome abnormalities. It has been estimated that annually over 1.25 million cases of blood cancer occur worldwide. The snoRNAs often show a differential expression profile in blood malignancies. Recent reports associate the abnormal expression of snoRNAs with the inhibition of apoptosis, uncontrolled cell proliferation, angiogenesis, and metastasis. This implies that targeting snoRNAs could be a potential way to treat hematologic malignancies. In this review, we describe the various functions of snoRNAs, their role in hematopoiesis, and the consequences of their dysregulation in blood malignancies. We also evaluate the potential of the dysregulated snoRNAs as biomarkers and therapeutic targets for blood malignancies.

Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome

“…DDX41 is also reported to promote the processing of small nucleolar RNA (snoRNA) from introns [ 75 ]. Some snoRNA are coded within introns of ribosomal protein genes and mature after being processed from the introns [ 87 , 88 ]. snoRNAs are classified into boxC/D type and boxH/ACA types depending on their sequences; the former catalyzes 2′-O-methylation and the latter is responsible for catalyzing the pseudouridylation of uridine residues in ribosomal RNA, thereby promoting ribosomal biogenesis.…”

Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential

“…SNORD42 is a diagnostic marker of AML. SNORD112-114 is mainly associated with leukemias based on stem cell pluripotency [64][65][66][67]. The expression of SNORD33, SNORD66, and SNORD76 in the plasma is significantly enhanced in non-small cell lung cancer (NSCLC) compared with that in healthy individuals.…”

The Role of Non-Coding RNAs in Myelodysplastic Neoplasms

“…In HSCs, snoRNAs expression is supposed to be cell-type-specific and play an important role in cell homeostasis, self-renewal, and stress response, while their aberrant expression has been linked to several hematological malignancies, MDS included [147][148][149]. For example, DDX41 regulates snoRNA processing, ribosomal biogenesis, and protein synthesis in hematopoietic stem and progenitor cells (HSPCs) and its germline mutation is known to confer predisposition to clonal myeloid disorders.…”