Masahiko Ajiro
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View article: A zebrafish model of chronic heart failure caused by protein aggregation in heart valves
A zebrafish model of chronic heart failure caused by protein aggregation in heart valves Open
We previously developed a unique zebrafish, tomato , expressing the red fluorescent protein DsRed under the control of the tph2 promoter. Unexpectedly, the tomato fish showed cardiac dilation and symptoms resembling those of chronic heart …
View article: Supplementary Figures S1-S10 from Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition
Supplementary Figures S1-S10 from Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition Open
Fig. S1: Sub-fractionation of MM cells by flow cytometry, Fig. S2: Detection of clonal repertoire in MM subfractions, Fig. S3: Heterogeneity of MM cells and cell surface marker gene expression, Fig. S4: DEGs in CD138+ and sCD138…
View article: Data from Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition
Data from Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition Open
The molecular basis of therapy resistance in multiple myeloma remains poorly understood. In this study, we performed single-cell RNA sequencing coupled with VDJ-targeted sequencing of highly purified primary multiple myeloma cells from pat…
View article: Supplementary Tables S1-S9 from Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition
Supplementary Tables S1-S9 from Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition Open
Supplementary Table S1: Patient information, Table S2: DEGs upregulated in CD138+ and CD138− MM cells detected in bulk RNA-seq, Table S3: DEGs in each cluster detected in scRNA-seq, Table S4: List of sgRNAs used in CR…
View article: Characterization of a Splice-Altering Variant in <i>SCN5A</i> Associated With Brugada Syndrome ― Insights Into Splice Error Correction ―
Characterization of a Splice-Altering Variant in <i>SCN5A</i> Associated With Brugada Syndrome ― Insights Into Splice Error Correction ― Open
We confirmed a splice site alteration by SCN5A c.1338G>A and propose extended use of SpliceAI for screening a target genomic region. The attempts to correct mis-splicing near the canonical splice site were not entirely successful, so furth…
View article: Zika virus reprograms the host tRNA epitranscriptome to adapt translation to A-ending codon bias
Zika virus reprograms the host tRNA epitranscriptome to adapt translation to A-ending codon bias Open
The codon usage bias of the Zika virus (ZIKV) genome is skewed towards AA-ending codons, which are preferentially decoded by U34-modified cognate tRNAs. This contrasts with the human host’s preference for AG-ending codons, suggesting that …
View article: Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing
Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing Open
Pathogenic RNA splicing variants have emerged as promising therapeutic targets due to their role in disease while preserving coding sequences. In this study, we developed RECTAS-2.0, a small molecule designed to correct RNA mis-splicing ca…
View article: SRSF3 is oncogenic in breast but tumor-suppressive in liver by differential regulation of gene expression
SRSF3 is oncogenic in breast but tumor-suppressive in liver by differential regulation of gene expression Open
SRSF3 (SRp20) is an essential splicing factor. We discovered Srsf3 plays an oncogenic role in breast cancer and Srsf3 knockout (KO) in mammary glands delays the development of breast cancer in an Erbb2 mouse model. In contrast, Srsf3 is tu…
View article: Switching of OAS1 splicing isoforms overcomes SNP-derived vulnerability to SARS-CoV-2 infection
Switching of OAS1 splicing isoforms overcomes SNP-derived vulnerability to SARS-CoV-2 infection Open
View article: Genotype-integrated single-cell transcriptome analysis of a myelodysplastic neoplasm case reveals the role of DDX41 p.R525H
Genotype-integrated single-cell transcriptome analysis of a myelodysplastic neoplasm case reveals the role of DDX41 p.R525H Open
DEAD-box helicase 41 (DDX41) is a key gene in germline-predisposed myeloid neoplasms, where pathogenic germline variants often lead to disease after acquiring a somatic mutation in trans. We conducted single-cell RNA sequencing combined wi…
View article: Data from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Data from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia Open
Purpose: Cervical cancer is one of the leading causes of cancer-related deaths among women worldwide. The purpose of this study is to assess the therapeutic effect of the newly developed cyclin-dependent kinase 9 (CDK9) inhibitor FI…
View article: Supplementary Figure legends (Figure S1-S7) from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Supplementary Figure legends (Figure S1-S7) from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia Open
Supplementary Figure legends (Figure S1-S7)
View article: Supplementary Figure legends (Figure S1-S7) from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Supplementary Figure legends (Figure S1-S7) from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia Open
Supplementary Figure legends (Figure S1-S7)
View article: Figure S1-S7, Table S1-S5 from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Figure S1-S7, Table S1-S5 from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia Open
Figure S1-S7, Table S1-S5
View article: Data from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Data from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia Open
Purpose: Cervical cancer is one of the leading causes of cancer-related deaths among women worldwide. The purpose of this study is to assess the therapeutic effect of the newly developed cyclin-dependent kinase 9 (CDK9) inhibitor FI…
View article: Figure S1-S7, Table S1-S5 from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia
Figure S1-S7, Table S1-S5 from CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has a Therapeutic Effect on HPV-Induced Neoplasia Open
Figure S1-S7, Table S1-S5
View article: PDIVAS: Pathogenicity predictor for Deep-Intronic Variants causing Aberrant Splicing
PDIVAS: Pathogenicity predictor for Deep-Intronic Variants causing Aberrant Splicing Open
Deep-intronic variants often cause genetic diseases by altering RNA splicing. However, these pathogenic variants are overlooked in whole-genome sequencing analyses, because they are quite difficult to segregate from a vast number of benign…
View article: Chemical induction of splice-neoantigens attenuates tumor growth in a preclinical model of colorectal cancer
Chemical induction of splice-neoantigens attenuates tumor growth in a preclinical model of colorectal cancer Open
Neoantigen production is a determinant of cancer immunotherapy. However, the expansion of neoantigen abundance for cancer therapeutics is technically challenging. Here, we report that the synthetic compound RECTAS can induce the production…
View article: 79. Deep intronic mutation in patients with adenosine deaminase 2 deficiency
79. Deep intronic mutation in patients with adenosine deaminase 2 deficiency Open
Background: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive inflammatory disease caused by loss-of-function mutations in the ADA2 gene. Most patients with DADA2 exhibit systemic vasculopathy consisten…
View article: Author Correction: Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia
Author Correction: Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia Open
View article: Switching of OAS1 splicing isoforms mitigates SARS-CoV-2 infection
Switching of OAS1 splicing isoforms mitigates SARS-CoV-2 infection Open
Background The rapidly accumulating disease susceptibility information collected from coronavirus disease (COVID-19) patient genomes must be urgently utilized to develop therapeutic interventions for SARS-CoV-2 infection. Chromosome 12q24.…
View article: Mechanism-Based Personalized Medicine for Cystic Fibrosis by Suppressing Pseudo Exon Inclusion
Mechanism-Based Personalized Medicine for Cystic Fibrosis by Suppressing Pseudo Exon Inclusion Open
View article: Identification of therapeutic small molecule compound for cystic fibrosis by targeting pseudo exon-inclusion
Identification of therapeutic small molecule compound for cystic fibrosis by targeting pseudo exon-inclusion Open
Background: Cystic fibrosis (CF) is an autosomal recessive rare genetic disease with approximately 70,000 patients in the world. The pathogenesis of CF is attributable to ～2,000 of known mutation within the CFTR gene, which interfere with …
View article: CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has Therapeutic Effect on HPV-Induced Neoplasia
CDK9 Inhibitor FIT-039 Suppresses Viral Oncogenes E6 and E7 and Has Therapeutic Effect on HPV-Induced Neoplasia Open
Background: Cervical cancer is one of the leading cause of cancer deaths among women worldwide, and human papillomavirus (HPV) infection is the etiology in more than 95% of cases. HPV induces tumorigenesis through viral oncogenes E6 and E7…
View article: A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells
A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells Open
Alternative RNA splicing is an essential process to yield proteomic diversity in eukaryotic cells, and aberrant splicing is often associated with numerous human diseases and cancers. We recently described serine/arginine-rich splicing fact…
View article: Vemurafenib-resistant BRAF selects alternative branch points different from its wild-type BRAF in intron 8 for RNA splicing
Vemurafenib-resistant BRAF selects alternative branch points different from its wild-type BRAF in intron 8 for RNA splicing Open
View article: E6^E7, a Novel Splice Isoform Protein of Human Papillomavirus 16, Stabilizes Viral E6 and E7 Oncoproteins via HSP90 and GRP78
E6^E7, a Novel Splice Isoform Protein of Human Papillomavirus 16, Stabilizes Viral E6 and E7 Oncoproteins via HSP90 and GRP78 Open
Transcripts of human papillomavirus 16 (HPV16) E6 and E7 oncogenes undergo alternative RNA splicing to produce multiple splice isoforms. However, the importance of these splice isoforms is poorly understood. Here we report a critical role …
View article: MOESM1 of Vemurafenib-resistant BRAF selects alternative branch points different from its wild-type BRAF in intron 8 for RNA splicing
MOESM1 of Vemurafenib-resistant BRAF selects alternative branch points different from its wild-type BRAF in intron 8 for RNA splicing Open
Additional file 1: Table S1. BRAF primers used in this study.
View article: Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates
Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates Open
Gene silencing techniques are widely used to control gene expression and have potential for RNAi-based therapeutics. In this report, transgenic mouse lines were created for conditional knockdown of Srsf3 (SRp20) expression in liver and mam…