Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control

Abstract

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP-RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

Long noncoding RNA MAPKAPK5‐AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

“…Many lncRNAs can regulate the expression of downstream target genes by forming complexes with RNA‐binding proteins, then acts as an oncogene or a suppressor oncogene . In this study, we found that knockdown of MAPKAPK5‐AS1 in CRC cells could lead to changes in related downstream genes, including p15 , p21 , p27 , p57 , KLF2 , and Trail .…”

“…In this study, we analyzed 2 sources Many lncRNAs can regulate the expression of downstream target genes by forming complexes with RNA-binding proteins, [27][28][29][30] then acts as an oncogene or a suppressor oncogene. [31][32][33][34][35] In this study, we found that knockdown of MAPKAPK5-AS1 in CRC cells could lead to changes in related downstream genes, including p15, p21, p27, p57, KLF2, and Trail. Among them, p21 has high basal expression abundance in CRC cells, which aroused our interest.…”

Transcriptomic Analysis Identifies RNA Binding Proteins as Putative Regulators of Myelopoiesis and Leukemia

“…Considering the complexity of the RBP expression profile during normal myeloid differentiation, it is apparent that dysregulation of this axis will contribute to leukemic transformation and maintenance. Recent reports showed that dysregulation of the PTGR networks on RBP genes contributes to oncogenesis in leukemia (9, 11). To understand the RBP gene expression landscape during leukemic transformation, we performed both gene-gene correlation and DGE analysis in the context of normal myelopoiesis and compared HSCs with LSCs and leukemic blast cells.…”

“…Wang et al has reported cancer-type-specific driver mutations and SCNAs in RBPs (5). Mutations in various RBPs splicing factors such as SRSF2, SF3B1 and U2AF1 have been reported to contribute to myelodysplasia, AML and other blood-related disorders owing to altered binding capacity and dysregulated splicing events (6–9). Mutations in the ribosomal RBP, RPS14, contribute to myelodysplasia owing to defective 18S rRNA processing (10).…”

HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells

“…hile extensive research has revealed the crucial importance of transcriptional regulation, the role for post-transcriptional processes in the function of normal and cancer stem cells remains poorly defined. RNA binding proteins (RBPs) provide control of mRNA metabolism and translation of key regulators that mediate stem cells' self-renewal and cell fate decisions 1,2 . Moreover, mutations and aberrant expression of RBPs have recently been implicated in multiple types of cancer, demonstrating the crucial role for RBPs in tumorigenesis [3][4][5][6][7][8][9] .…”