Ask about this productRelated genes to: SLU7 Blocking Peptide
- Gene:
- SLU7 NIH gene
- Name:
- SLU7 homolog, splicing factor
- Previous symbol:
- -
- Synonyms:
- 9G8
- Chromosome:
- 5q33.3
- Locus Type:
- gene with protein product
- Date approved:
- 2006-11-27
- Date modifiied:
- 2015-07-30
Related products to: SLU7 Blocking Peptide
Related articles to: SLU7 Blocking Peptide
- Cancer treatment remains challenging due to heterogeneous responses to immunotherapy across patients and tumor types. Innovative strategies are required to overcome immune evasion. We have identified the splicing factor SLU7 as essential for the survival of cancer cells from diverse origins. SLU7 knockdown induces R-loop accumulation, transcription-dependent genomic instability, DNA damage, and replication catastrophe, together with aberrant splicing and inhibition of nonsense-mediated mRNA decay (NMD) and/or DNA methylation. These alterations lead to the expression of neoantigens, interferon B1, endogenous retroviruses, and cancer-testis antigens, which would enhance tumor immunogenicity. Therefore, we propose SLU7 targeting as a dual-action therapy, combining direct tumor suppression with immune activation. We used organoids and various murine cancer models, including orthotopic liver tumors, and multiple molecular strategies, such as inducible CRISPR/Cas9 and shRNA, systemic delivery of chimeric siSLU7-nucleolin aptamers (APTASLU), and intratumoral injection of siSLU7-loaded nanoparticles alone or in combination with the immune checkpoint inhibitor anti-PD1. We show that distinct siSLU7 sequences and delivery platforms effectively inhibit the growth of tumors including liver orthotopic and human hepatocellular carcinoma, cholangiocarcinoma and colon carcinoma subcutaneous xenografts. Furthermore, SLU7 silencing may synergize with immune checkpoint inhibitors, amplifying anti-tumor responses. Our in vivo data demonstrate that SLU7 is a promising, versatile target for possibly diverse cancers. Its multimodal mechanism offers potential to overcome tumor heterogeneity, reverse immune tolerance, and enhance immunotherapy efficacy. - Source: PubMed
Publication date: 2025/12/02
Rojo CarlaOtero AaronElizalde MariaAzkona MariaBarbero RobertoLatasa Maria UUriarte IkerGutierrez-Uzquiza AlvaroAlignani DiegoGuembe LauraLujambio AmaiaPastor FernandoFernández-Barrena Maite GÁvila Matias AArechederra MariaBerasain Carmen - Induction of ferroptosis is a potential strategy to eliminate chemotherapy-resistant acute myeloid leukemia (AML) cells. Here, we investigate the role and mechanism of thyroid hormone receptor-associated protein 3 (THRAP3) in ferroptosis of AML cells. We show that high expression of THRAP3 is correlated with a poor prognosis in AML patients. THRAP3 knockdown suppresses AML cell proliferation, and delays orthotopic and subcutaneous tumor growth in male mice; however, THRAP3 overexpression exerts the opposite roles. THRAP3 overexpression promotes resistance of AML cells to RSL3/erastin-induced ferroptosis via inhibiting iron accumulation and promoting GSH synthesis. Mechanistically, THRAP3 recruits SLU7 homolog, splicing factor (SLU7) to facilitate GIT ArfGAP 2 (GIT2) Exon14 skipping. Inhibition of GIT2 Exon14 skipping reverses THRAP3-induced ferroptosis resistance in vitro and in vivo. Altogether, THRAP3 contributes to ferroptosis resistance of AML cells via interaction with SLU7 to trigger GIT2 Exon14 skipping, which suggests THRAP3 to be a therapeutic target for AML. - Source: PubMed
Publication date: 2025/12/01
Wang DanWu ZhixiangLiu SiyangHe JingZhang HaixiaChen PanYang Minghua - The DExD/H-box RNA helicase Prp22 catalyzes messenger RNA (mRNA) release from the spliceosome, and has also been implicated in proofreading the 3' splice site (3'SS), preventing exon ligation of mutant pre-mRNAs through an ATP-dependent mechanism. However, here we reveal an unexpected role for Prp22 in promoting exon ligation of both wild-type and mutant pre-mRNAs by stabilizing Slu7's association with the spliceosome prior to exon ligation. Notably, ATP binding, rather than hydrolysis, by Prp22 inhibits exon ligation of 3'SS mutant pre-mRNA. Following exon ligation, Prp22-mediated ATP hydrolysis facilitates the dissociation of both Slu7 and mRNA from the spliceosome. Remarkably, Prp22 and Cwc22, which bind the 3'- and 5'-exons respectively, remain associated with the released mRNA, whereas Slu7 and Fyv6 dissociate independently. We propose that Prp22 facilitates exon ligation by stabilizing Slu7 binding, with binding of ATP by Prp22 potentially destabilizing that interaction, thereby weakening contacts between the 5'-exon and the 3'SS to inhibit exon ligation. After exon ligation, Prp22-driven ATP hydrolysis induces a conformational change in Prp8 that disrupts its interdomain interactions, enabling mRNA release through the domain interfaces, with Prp22 and Cwc22 remaining associated with the released mRNA. - Source: PubMed
Chung Che-ShengTseng Chi-KangChen Hsin-ChouCheng Soo-Chen - How the ubiquitously expressed splicing factors specifically regulate neural crest (NC) development and enhance their vulnerability to splicing perturbations remain poorly understood. Here, we show that NC-specific DLC1, partnering with SF3B1-PHF5A splicing complex, are crucial for determining avian trunk NC cell fate by regulating the splicing of NC specifiers SOX9 and SNAI2 pre-mRNAs rather than their upstream regulators BMP4, WNT1, and PAX7. Mechanistically, SF3B1-PHF5A binds to the intronic branch site (BS) sequences of all factors, while DLC1 interacts with a specific motif near the BS sequences of SOX9 and SNAI2, thereby determining their functional specificity in NC specification. Moreover, DLC1 increases NC cells' vulnerability to splicing modulator pladienolide B (PB) by reducing the binding capacity of the SF3B1-PHF5A splicing complex to the shorter length of both SOX9 intron 2 and SNAI2 intron 1, which possess weaker polypyrimidine tract 3' of the BS sequence, resulting in intron retention and loss of NC progenitors. Conversely, somite specific SLU7-SF3B1-PHF5A splicing complex regulates SOX9 and SNAI2 expression and imparts resistance to PB. Our data reveal the cell-type specific splicing complexes with distinct vulnerabilities to PB, highlighting the critical role of the DLC1-SF3B1-PHF5A in determining trunk NC cell fate and enhancing its susceptibility to splicing perturbation. - Source: PubMed
Publication date: 2025/07/21
Zheng ZhengfanGuo SuisuiTam Hoi YauWang JingkaiRao YanxiaHui Man-NingCheung May Pui LaiLeung Alan Wai LunWong Kelvin K WSharma RakeshLiu Jessica AijiaCheung Martin - The nuclear RNA exosome complex is crucial for noncoding RNA processing and RNA quality control in the nucleus. Identifying substrates and intermediates of RNA decay pathways, such as those mediated by the exosome complex using Oxford Nanopore sequencing can be difficult in part because a simple method to detect them has been lacking and also because some of these RNAs lack abundant poly(A) tails which are required for Oxford Nanopore-based sequencing. Here we describe an Oxford nanopore-based approach which can be used to identify long reads corresponding to precursors and products of nuclear exosome processing. We are able to observe accumulation of unprocessed snoRNAs, cleavage products of the yeast nuclear RNase III endonuclease Rnt1p when the nuclear exosome component Rrp6p is inactivated. - Source: PubMed
He KevinChanfreau Guillaume F