Table 1-.
Summary of splicing regulators and their roles in normal hematopoiesis from recent publications.
| Splicing regulators | Description | Animal model and hematopoietic phenotypes |
|---|---|---|
| SF3B1 | SF3B1 is a component of the U2 snRNP that recognizes branch point, and promotes the binding of U2 snRNA to the branchpoint [11,12,23,24]. | Germline Sf3b1+/− murine model; Sf3b1 haploinsufficiency decreases HSC repopulating potential but does not increase ring sideroblast formation [27,28]. |
| U2AF1 | U2AF1 is a member of the U2AF heterodimer involved in the recognition of AG-dinucleotide at the 3’ splice site during pre-mRNA splicing [29–31]. |
U2af1fl/fl;Mx1-Cre murine model; Loss of U2af1 causes detrimental effects on HSC function and normal hematopoiesis [32*]. |
| SRSF2 | SRSF2 is a member of the serine/arginine-rich (SR) protein family involved in exon inclusion by binding to specific exonic splicing enhances (ESE) sequences [34–39]. |
Srsf2fl/fl;Mx1-Cre murine model; Srsf2 deletion leads to leukopenia, anemia, and bone marrow aplasia and compromised HSC self-renewal [39]. |
| ZRSR2 | ZRSR2 is a component of the minor spliceosome and primarily responsible for the U12 type minor intron excision [6,8]. |
Zrsr2fl/fl;Mx1-Cre murine model; Loss of Zrsr2 increases HSC number and self-renewal capability [40**]. |
| Breast carcinoma amplified sequence （BCAS2） | BCAS2 is a component of Prp19 complex involved in spliceosome assembly [44]. |
bcas2−/− zebrafish model; Bcas2 deletion causes severe defects in HSC function and definitive hematopoiesis [47]. |
| Protein arginine methyltransferase 5 (PRMT5) | PRMT5 mediates symmetric demethylation of arginines (SDMA) on Sm (D1, B/B, D3) proteins, a modification required for spliceosome assembly [51]. |
Prmt5fl/fl;Mx1-Cre murine model; Loss of Prmt5 decreases HSC quiescence leading to HSC exhaustion [54*]. |
| DEAD-box Helicase 41 (DDX41) | DDX41 is an RNA helicase that interacts with spliceosome components and is implicated in regulating pre-mRNA splicing [55]. |
ddx41sa14887 zebrafish model; Loss-of-function Ddx41 results in increased rate of endothelial-to-hematopoietic transition (ETH) and HSPC expansion and suppresses the expansion and differentiation of erythroid progenitors [57**,58]. |