Ask about this productRelated genes to: RRAGD Blocking Peptide
- Gene:
- RRAGD NIH gene
- Name:
- Ras related GTP binding D
- Previous symbol:
- -
- Synonyms:
- DKFZP761H171, bA11D8.2.1
- Chromosome:
- 6q15
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-07
- Date modifiied:
- 2016-02-23
Related products to: RRAGD Blocking Peptide
Related articles to: RRAGD Blocking Peptide
- Autosomal dominant kidney hypomagnesemia with RRAGD variants (ADKH-RRAGD) is a hereditary disorder characterized by kidney tubulopathy and dilated cardiomyopathy (DCM). RagD, encoded by the RRAGD gene, is a small GTPase involved in activating the mechanistic target of rapamycin complex 1 (mTORC1) by amino acids. Although several gain-of-function variants in the RRAGD gene have been identified, their contributions to DCM remain unclear. Here, we hypothesize that these RRAGD variants induce mTORC1 overactivation, thereby contributing to the manifestation of DCM. To investigate this, we established T-REx HeLa cell lines that overexpress the RRAGD p.(Ser76Leu) or the wild-type (WT) variant to assess the effects on mTORC1 signaling. Additionally, we developed the first cellular model of ADKH-RRAGD utilizing genetically edited human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express the mutated variant. Our data indicate that the RRAGD p.(Ser76Leu) variant maintains the phosphorylation of mTORC1 targets (i.e., S6K, 4E-BP1, and TFEB) during amino acid starvation, in contrast to RRAGD WT in T-REx HeLa cells. The pharmacological inhibition of mTOR with Torin1 reversed these changes. In 2D-cultured RRAGD hiPSC-CMs, mTORC1 remained responsive to amino acid starvation. Results from bulk RNA sequencing showed an upregulation of pathways associated with cytoskeletal organization and a downregulation of muscle development in RRAGD hiPSC-CMs. Moreover, a prolonged duration of Ca transients was observed in the mutant cardiomyocytes. Altogether, our data demonstrate that gain-of-function variants in RRAGD cause mTORC1 activation in T-REx HeLa cells. Consequently, cardiomyocytes develop impaired intracellular Ca clearance and activation of transcriptional programs, suggesting dedifferentiation. - Source: PubMed
Adella Anastasiavan Katwijk Sara BLeermakers Pieter Avan Ham Willem Bde Ruiter HestherIlgutytė JuditaHendrickx SuzanneNijland Levide Boer Teun Pvan Rooij EvaHoenderop Joost G Jde Baaij Jeroen H F - Aminoacyl-tRNA synthetases (ARSs) assemble into the multi-tRNA synthetase complex (MSC) to mediate noncanonical functions in cell signaling and stress responses. Among them, human cytosolic leucyl-tRNA synthetase 1 (LARS1) plays a central role in sensing leucine and activating mTORC1, thereby linking nutrient availability to metabolic regulation. Despite recent progress, fundamental questions remain unresolved about the regulatory mechanisms governing LARS1's non-canonical functions, particularly its structural organization within the MSC. Here, we employ an integrated approach combining structural, biochemical, and cellular analyses to investigate the noncanonical roles of LARS1. The cryo-EM structure of the LARS1:isoleucyl-tRNA synthetase 1 (IARS1) complex reveals that LARS1 binds to IARS1, its anchoring partner in the MSC, via its UNE-L domain. Amino acid stimulation induces LARS1 phosphorylation at Ser1070, Ser1077, and Ser1082, which are located at the interface with IARS1. These modifications disrupt the interaction, promote LARS1 dissociation from the MSC, and enable mTORC1 activation. This study highlights phosphorylation as a conserved and critical molecular switch that orchestrates the non-canonical functions of MSC by dynamically modulating the assembly and activity of its components in response to external stimuli. - Source: PubMed
Publication date: 2026/06/11
Kim YoujinKim Joo-ChanKim Do-WookKim JinwooChoi JaehunPark Seo YoungLee JiminYoon InaKim SunghoonKang Jin YoungPark Hee-Sung - -Methyladenosine (mA) is primarily enriched in the last exons and 3' untranslated regions (3'UTRs) of messenger RNAs (mRNAs) and is associated with T cell homeostasis. Upon T cell activation, global mRNA 3'UTR shortening is facilitated through alternative polyadenylation (APA). However, it is unclear how T cells coordinate these two important posttranscriptional regulatory events to maintain quiescence. Here, we found that the mA "writer" METTL3 directly interacts with APA factor NUDT21 and guided poly(A) site selection. Deletion of in T cells resulted in simultaneous overactivation and accelerated apoptosis, leading to T cell loss and impaired adaptive immune function. Mechanistically, METTL3 recruits NUDT21 to the proximal poly(A) site of mRNA, generating long 3'UTR with mA modifications. deficiency causes 3'UTR shortening and increases expression, leading to overactivation of mammalian target of rapamycin signaling. Our study reveals an mA-guided poly(A) site selection mechanism and defines in vivo roles of mA-APA cross-talk in maintaining T cell quiescence. - Source: PubMed
Publication date: 2026/05/13
Zhang XingliLi HaixinWang GaoyangMiao ShanHao YajuanLi SongLi BinXiao HuiSu BingWu YuzhangYe YouqiongLi Hua-Bing - - Source: PubMed
Publication date: 2026/04/21
Zhang ZongyeWang HongboCheng XingboZhang ZhichangHou ZhenxingLiu ZhendongGao Yanzheng - This study aimed to identify autophagy-related genes with a causal role in ischemic stroke (IS) risk using a multi-omics Mendelian randomization (MR) approach. We integrated summary-level data for blood-derived DNA methylation (mQTLs), expression (eQTLs), and protein (pQTLs) quantitative trait loci for 594 autophagy-related genes with large-scale IS genome-wide association studies for discovery (GCST006908) and validation (FinnGen). Summary-data-based MR (SMR) with colocalization analysis was performed, supplemented by brain eQTL analysis, protein-protein interaction networking, and drug prediction. The analysis identified 113 mQTLs, 38 eQTLs, and 9 pQTLs associated with IS risk, with colocalization supporting shared causal variants for a subset. Validation in FinnGen confirmed 13 mQTLs and 2 eQTLs, notably involving genes like CDKN1A, RRAGD, and SLC35D3. Multi-omics integration revealed regulatory cascades - for example, methylation at cg17245862 influencing DYNLT1 expression and protein levels. Brain-specific eQTL analysis supported 10 genes, including DYNLT1. Protein-protein interaction network analysis highlighted hub genes such as CDKN1A, PARK7, and LEP. Drug prediction suggested N-Acetyl-L-cysteine and acetaminophen as potential modulators targeting these genes. This study provides evidence for a potential causal role of autophagy-related genes and molecular traits in IS development, notably DYNLT1. Further research focusing on robustly identified candidates is warranted. - Source: PubMed
Nie HaoZhang LiHei YunpengMa TaoXu XinZhang Maoxian