Genomic analyses of the myeloid malignancies and clonal disorders of hematopoiesis that may give rise to these disorders have identified that mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are among the most common targets of somatic mutations. These spliceosomal mutations often occur in a mutually exclusive manner with one another and, in aggregate, account for the most frequent class of mutations in patients with myelodysplastic syndromes (MDSs) in particular. Although substantial progress has been made in understanding the effects of several of these mutations on splicing and splice site recognition, functional connections linking the mechanistic changes in splicing induced by these mutations to the phenotypic consequences of clonal and aberrant hematopoiesis are not yet well defined. This review describes our current understanding of the mechanistic and biological effects of spliceosomal gene mutations in MDSs as well as the regulation of splicing throughout normal hematopoiesis.
Enzymatic defect in "X-linked" sideroblastic anemia: molecular evidence for erythroid delta-aminolevulinate synthase deficiency
Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A)
Inhibition of msl-2 splicing by Sex-lethal reveals interaction between U2AF35 and the 3' splice site AG
Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation.
An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer.
Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16
Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis
Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay
The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload
A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons
Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts
The U2AF35-related protein Urp contacts the 3' splice site to promote U12-type intron splicing and the second step of U2-type intron splicing
QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates cancer cell proliferation
The transporter ABCB7 is a mediator of the phenotype of acquired refractory anemia with ring sideroblasts
A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events
Depletion of Sf3b1 impairs proliferative capacity of hematopoietic stem cells but is not sufficient to induce myelodysplasia.
Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron.
MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation
Transcriptome sequencing reveals potential mechanism of cryptic 3' splice site selection in SF3B1-mutated cancers
A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis.
Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point
Diagnosis and treatment of sideroblastic anemias: from defective heme synthesis to abnormal RNA splicing
Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage
Splicing factor gene mutations in the myelodysplastic syndromes: impact on disease phenotype and therapeutic applications
CD19 Isoforms Enabling Resistance to CART-19 Immunotherapy Are Expressed in B-ALL Patients at Initial Diagnosis
Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes
Degenerate minigene library analysis enables identification of altered branch point utilization by mutant splicing factor 3B1 (SF3B1)
BCAS2 is essential for hematopoietic stem and progenitor cell maintenance during zebrafish embryogenesis.
The splicing factor U2AF1 contributes to cancer progression through a noncanonical role in translation regulation
Anti-tumor efficacy of a novel CLK inhibitor via targeting RNA splicing and MYC-dependent vulnerability
Human PRPF40B regulates hundreds of alternative splicing targets and represses a hypoxia expression signature
Cancer-Associated Substitutions in RNA Recognition Motifs of PUF60 and U2AF65 Reveal Residues Required for Correct Folding and 3' Splice-Site Selection
U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies
Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis
Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies
Alternative splicing and cancer: insights, opportunities, and challenges from an expanding view of the transcriptome.
Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing
The cancer-associated U2AF35 470A>G (Q157R) mutation creates an in-frame alternative 5' splice site that impacts splicing regulation in Q157R patients
Machine learning demonstrates that somatic mutations imprint invariant morphologic features in myelodysplastic syndromes.
Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer
Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.