Ask about this productRelated genes to: RBM39 Blocking Peptide
- Gene:
- RBM39 NIH gene
- Name:
- RNA binding motif protein 39
- Previous symbol:
- RNPC2
- Synonyms:
- CC1.3, HCC1, CAPER, fSAP59, CAPERalpha
- Chromosome:
- 20q11.22
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-21
- Date modifiied:
- 2014-11-19
Related products to: RBM39 Blocking Peptide
Related articles to: RBM39 Blocking Peptide
- Pancreatic ductal adenocarcinoma (PDAC) remains a formidable clinical challenge. Next-generation protein arginine methyltransferase 5 (PRMT5) inhibitors show promising clinical results in a subset of PDACs with co-deletion of the tumor suppressor CDKN2A and the methylthioadenosine phosphorylase (MTAP) gene, but resistance limits their efficacy. Our study suggests that compensatory spliceosomal reprogramming contributes to adaptation to PRMT5 inhibition. Through comprehensive molecular profiling, we demonstrate that PRMT5 inhibitors induce upregulation of RNA-binding proteins, including RNA-binding protein 39 (RBM39). We investigated whether this response could be therapeutically leveraged by combining PRMT5 inhibition with Indisulam-mediated RBM39 degradation, which yielded synergistic activity in cellular model systems. The combination strategy significantly enhanced apoptotic cell death and suppressed tumor outgrowth in resistance assays compared to single-agent treatments. Multi-omics analysis revealed concomitant suppression of DNA repair and metabolic pathways. Collectively, our work support spliceosomal rewiring as a candidate adaptive response to PRMT5 inhibition and nominates RBM39 as a candidate therapeutic vulnerability, thereby supporting further evaluation of dual targeting of the splicing machinery. - Source: PubMed
Publication date: 2026/08/12
Spielmann ValentinaBuchloh JonasSelcen SelenSchneider CarolinJansari ShaishaviFang XinDuan NingjunDemirdizen EnginKrauß LukasEggert JessicaSiegfried GeraldineFedou SandrineLenz ChristofWieland LenaConradi Lena-ChristinReichert MaximilianEllenrieder VolkerGhadimi MichaelGrade MarianHessmann ElisabethKhatib Abdel-MajidBraun Christian JWegwitz FlorianSaur DieterWirth MatthiasSchneider Günter - The unfolded protein response (UPR) preserves endoplasmic reticulum proteostasis through coordinated signaling pathways, including the IRE1α-XBP1 axis, which promotes adaptive transcriptional programs via noncanonical XBP1 mRNA splicing. However, upstream mechanisms regulating this pathway remain incompletely defined. Here, we apply CRASP-seq, a scalable RNA-coupled CRISPR screening platform, to systematically identify regulators of XBP1 splicing. We uncovered the U2 snRNP auxiliary factor RBM39 as a critical positive regulator of this process. Perturbation of RBM39 or U2 snRNP components induces alternative splicing of , leading to exon-18 skipping and the production of an unstable transcript subject to nonsense-mediated decay, as well as a truncated IRE1α isoform that acts in a dominant-negative manner to suppress XBP1 splicing. Mechanistically, we show that heat shock reduces RBM39 functional activity and promotes exon-18 skipping, thereby attenuating IRE1α-XBP1 signaling. Functionally, hyperactivation of this pathway is detrimental under proteotoxic stress, suggesting that exon-18 skipping serves as a stress-adaptive mechanism to limit UPR output. Together, our findings reveal a previously unrecognized regulatory axis linking the canonical splicing machinery to UPR signaling and establish alternative splicing of as a key modulator of cellular stress responses. - Source: PubMed
Publication date: 2026/08/07
Kim Jeongjin JBehera Amit KDamodaran Arun PrasathKordale ShreyaGonatopoulos-Pournatzis Thomas - Medication-related osteonecrosis of the jaw is a severe adverse effect of antiresorptive agents. Although autologous mesenchymal stromal cell therapy is a potential treatment, the effects of medication-related osteonecrosis of the jaw microenvironment on mesenchymal stromal cells remain unclear. - Source: PubMed
Publication date: 2026/07/26
Nishimaki KazuhiroPark Sung-JoonKaibuchi NobuyukiOnizuka SatoruOkamoto ToshihiroNakai KentaYamato Masayuki - Targeted protein degradation is an emerging approach that utilizes cellular degradation pathways to inhibit a target protein. Small molecules such as molecular glues or PROTACs can be used to mediate the formation of a ternary complex with an E3 ligase and the target protein, which can dramatically enhance the degradation process. This approach is promising for cancer therapy, where degradation of oncogenic proteins can lead to cancer cell toxicity. To design new molecular glues, it is important to develop methods that predict how well a given molecule stabilizes a protein-protein interaction. However, conventional molecular dynamics simulations face challenges in capturing the long-time scale binding and unbinding events that would be used to evaluate this stabilization. In this study, we developed a strategy that allows us to evaluate the stability of protein-protein interactions in the presence of a glue molecule using weighted ensemble simulations in combination with weakened protein-protein interactions. Using this strategy, we generated unbinding trajectories of the DCAF15-RBM39 system with small molecules E7820, Indisulam, and several other Indisulam analogs. We were able to observe distinctly different behaviors between systems with different glues, which was in agreement with their reported EC50 values. We believe this approach could aid drug discovery efforts by expanding the set of druggable targets and improving the success rate of molecular glue development. - Source: PubMed
Atik Seref BerkDickson Alex - Ewing sarcoma (EwS) is a group of bone and soft-tissue cancers in children and young adults. Because EwS cells have pronounced sensitivity to radiation and chemotherapy-induced DNA damage, the oncoprotein EWS-FLI1 is likely to be involved in DNA repair. Here, we demonstrate that EWS-FLI1 causes a defect in microhomology-mediated end joining (MMEJ) repair. EWSR1 is a splicing factor that promotes the faithful splicing of the POLQ pre-mRNA, required for the expression of Polθ, a critical protein in the MMEJ pathway. Expression of EWS-FLI1 or depletion of EWSR1 causes increased POLQ exon 25 skipping, decreased Polθ expression, impaired MMEJ, and enhanced cellular sensitivity to inhibitors of the Fanconi anemia (FA), homologous recombination (HR), or non-homologous end joining (NHEJ) pathways, through the mechanism of synthetic lethality. Correction of POLQ exon 25 skipping restored Polθ expression and MMEJ activity in EwS. Inhibitors of the FA, HR, or NHEJ pathways may therefore provide a targeted therapy for EwS patients. - Source: PubMed
Publication date: 2026/07/21
Asada ShuheiZhu GuangliAbeykoon Jithma PrasadTanaka YutaroNguyen HuyHirohashi YunaIyer Divya RAshton Nicholas WilliamMukkavalli SirishaVelazquez MarthaJiang LigeDel Busso MilesThangaiah Judith JebastinRobinson Steven IParmar KalindiVan Allen Eliezer MGillani RiazShapiro Geoffrey ID'Andrea Alan D