Ask about this productRelated genes to: PUS1 Blocking Peptide
- Gene:
- PUS1 NIH gene
- Name:
- pseudouridine synthase 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 12q24.33
- Locus Type:
- gene with protein product
- Date approved:
- 2001-04-06
- Date modifiied:
- 2018-09-12
Related products to: PUS1 Blocking Peptide
Related articles to: PUS1 Blocking Peptide
- Pseudouridine (Ψ) modification is a prevalent epitranscriptomic mark with critical roles in carcinogenesis; however, the function of its catalytic "writer" enzyme, pseudouridine synthase 1 (PUS1), in renal cell carcinoma (RCC) remains elusive. Our analysis revealed that mRNA is upregulated in RCC and is associated with an unfavorable prognosis. Strikingly, this transcriptional upregulation results in a concomitant and exclusive increase in the protein abundance of PUS1 isoform 2. Mechanistically, although PUS1 markedly enhances global mRNA translation, this effect is not directly mediated via Ψ modification of either mRNA or tRNA. Instead, PUS1 regulates pre-mRNA splicing, and its deficiency induces elevated intron retention. This, in turn, culminates in the formation of double-stranded RNA (dsRNA), which subsequently activates the innate antiviral immune response and inhibits global translation. Furthermore, depletion of PUS1 in tumor cells significantly sensitizes RCC to immune checkpoint blockade therapy. Collectively, our findings demonstrate that PUS1 shields tumor cells from endogenous dsRNA accumulation and the consequent detrimental innate immune activation, thereby unveiling a novel and promising therapeutic strategy for RCC. - Source: PubMed
Publication date: 2026/03/25
Zhu ZiweiLu ZeyiLi FanXu ZhehaoWang RuyueLi YangLu HaohuaDing YimingLuo WenqinLin YudongLu YiMao XudongLi MengxuanWang ZiyuanDing LifengXia LiqunLi Gonghui - Transfer RNA-derived fragments (tRFs) are a recently discovered class of short noncoding RNAs widely distributed in various tissues and cell types. They are involved in the regulation of gene expression and play important roles in both physiological and pathological processes, garnering growing attention. However, the functions and underlying mechanisms of most tRFs in tumorigenesis and progression remain largely unclear. Through small RNA sequencing of nasopharyngeal carcinoma (NPC) and adjacent tissues, we found that among the top 30 highly expressed tRFs in NPC tissues, 13 were derived from lysine tRNAs, forming the 5′-tRF-Lys cluster. This cluster was found to promote NPC cell proliferation, invasion, and migration. Mechanistically, 5′-tRF-Lys binds to the 3′-untranslated region (3′-UTR) of messenger RNA (mRNA), suppressing its expression and thereby activating the Hippo/YAP signaling pathway to drive tumor progression. The elevated expression of pseudouridine synthases and in NPC tissues catalyzes pseudouridine modification of tRNA-Lys, facilitating its cleavage into 5′-tRF-Lys and accounting for its upregulation. Notably, the -targeting small-molecule inhibitor mogroside IV-e effectively reversed malignant phenotypes in both in vitro and in vivo NPC models. This study uncovers a novel mechanism in which pseudouridine synthases and drive the biogenesis of the tRF-Lys cluster, promoting NPC malignancy by suppressing and activating the Hippo/YAP signaling pathway. These findings highlight the therapeutic potential of targeting pseudouridine synthases to reduce tRF-Lys production as a novel strategy for NPC treatment. - Source: PubMed
Publication date: 2026/02/28
Ren DaixiYang MeiMo YongzhenYan QijiaShi LeiZhang ShanshanGong ZhaojianGuo CanZhou MingXiang BoTan MingLi GuiyuanChen PanXiong WeiZeng Zhaoyang - Pseudouridine (Ψ) is an abundant modification in small RNA catalyzed by multiple pseudouridine synthases (PUSs). However, the substrate specificity of human PUSs remains elusive. Here, we adopted PRAISE, a quantitative Ψ detection method, to profile pseudouridylation in small RNA, including cytosolic and mitochondrial tRNAs, snRNA, and snoRNA. We found that snoRNA pseudouridylation is mediated not only by RNA-guided DKC1, but also by the stand-alone enzyme PUS7 at a specific site. Interestingly, several PUS enzymes, including PUS1, RPUSD1, and PUS7, which install nearby Ψ sites within tRNA anticodon stem-loop, can influence pseudouridylation catalyzed by other PUSs, revealing an unrecognized interplay during Ψ formation. For the three RluA family enzymes, RPUSD1 catalyzes the canonical Ψ30 in tRNA-Ile and Ψ72 in tRNA-Arg isoacceptors. RPUSD2 pseudouridylates Ψ31 of mt-tRNA, Ψ32 of mt-tRNA and mt-tRNA, whereas RPUSD3 lacks tRNA activity. Together, our quantitative Ψ profiling characterized PUS tRNA substrates and revealed unexpected PUS interplay. - Source: PubMed
Publication date: 2026/02/16
Liu WenqingMa YichenWang LipingLu BoDong YuyangZhuang YuanHe BoZhang MeilingYi Chengqi - RNA modification enzymes (RMEs) are key post-transcriptional regulators that impact RNA stability, translation, and splicing. Dysregulation of RMEs is closely associated with tumor initiation and progression. However, their global regulatory patterns and clinical relevance across cancer types remain incompletely characterized. - Source: PubMed
Publication date: 2026/01/28
Zhan QianqianSun HuihuiWang XiangtingLiang Xiaolin - MLASA syndrome is a rare mitochondrial disorder that presents in three distinct genetic forms: MLASA1, MLASA2, and MLASA3; MLASA1 is the most common form. The clinical features include mitochondrial myopathy, lactic acidosis, and sideroblastic anemia. Although presence of other features is not uncommon, its association with long QT (LQT) syndrome has not been described before. In addition, while MLASA syndrome has been reported from several countries worldwide, we present the first patient with MLASA1 syndrome from the Kingdom of Saudi Arabia in this case report. The 10-year-old girl with history of poor health since infancy and recurrent hospital admissions for infections and blood transfusions was referred to our hospital for allogeneic bone marrow transplantation. Early in her childhood, she was diagnosed with symptomatic LQT syndrome and, at a later age, with sideroblastic anemia. Whole-exome sequencing (WES) revealed homozygous mutations in the gene and heterozygous mutations in the gene. The WES test of the parents was negative, and there was no family history suggestive of a similar diagnosis. Therefore, our patient has most probably developed the syndrome as a result of a sporadic mutation; however, the possibility of sex cell germline mosaicism cannot be excluded. Heterozygous gene mutation is associated with the development of type 1 LQT syndrome. Detection of the MLASA syndrome and proper intervention at an early age are crucial for successful management. Associated LQT syndrome should always be anticipated. Despite the presence of a fully tissue-matched sibling, the parents of our patient declined the option of allogeneic bone marrow transplantation due to potential severe cardiac and liver complications. - Source: PubMed
Publication date: 2026/01/19
Abbas Adil AbdelhamedMonagel Dania AdelAlthubaiti Sami Jowaiber