RRAG

Last update 08 May 2025

Basic Info

Synonyms

RAG GTPases

Introduction-

100 Clinical Results associated with RRAG

100 Translational Medicine associated with RRAG

0 Patents (Medical) associated with RRAG

674

Literatures (Medical) associated with RRAG

01 Jun 2025·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

POLR1D, a shared subunit of RNA polymerase I and III, modulates mTORC1 activity

Article

Author: Gorjão, Neuton ; Szczesny, Roman J ; Borowski, Lukasz S ; Graczyk, Damian

The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial nutrient sensor and a major regulator of cell growth and proliferation. While mTORC1 activity is frequently upregulated in cancer, the mechanisms regulating mTORC1 are not fully understood. POLR1D, a shared subunit of RNA polymerases I and III, is often upregulated in colorectal cancer (CRC) and mutated in Treacher-Collins syndrome. POLR1D, together with its binding partner POLR1C, forms a dimer that is believed to initiate the assembly of the multisubunit RNA polymerases I and III. Our data reveal an unexpected link between POLR1D and mTORC1 signalling. We found that the overproduction of POLR1D in human cells stimulates mTORC1 activity. In contrast, the downregulation of POLR1D leads to the repression of the mTORC1 pathway. Additionally, we demonstrate that a pool of POLR1D localises to the cytoplasm and interacts with the mTORC1 regulator RAGA and RAPTOR. Furthermore, POLR1D enhances the interaction between RAPTOR and RAGA and sustains mTORC1 activity under starvation conditions. We have identified a novel role for the RNA polymerase I/III subunit POLR1D in regulating mTORC1 signalling. Our findings suggest the existence of a new node in the already complex mTORC1 signalling network, where POLR1D functions to convey the cell's internal status, namely polymerase assembly, to this kinase.

04 May 2025·Autophagy

Induction of lysosome biogenesis is a novel function of the CGAS-STING1 pathway

Article

Author: Wan, Wei ; Xu, Yinfeng

Induction of macroautophagy/autophagy has been established as an important function elicited by the CGAS-STING1 pathway during pathogen infection. However, it remains unknown whether lysosomal activity within the cell in these settings is concurrently enhanced to cope with the increased autophagic flux. Recently, we discovered that the CGAS-STING1 pathway elevates the degradative capacity of the cell by activating lysosome biogenesis. Intriguingly, we found that STING1-induced GABARAP lipidation, rather than TBK1 activation, serves as the key mediator triggering the nuclear translocation of transcription factor TFEB and enhances the expression of lysosome-related genes. Mechanistically, we demonstrated that lipidated GABARAP on single membranes, regulated by the V-ATPase-ATG16L1 axis, sequesters the FLCN-FNIP complex to abolish its function toward RRAGC and RRAGD, leading to a specific impairment of MTORC1-dependent phosphorylation of TFEB and resulting in its subsequent nuclear translocation. Functionally, we showed that STING1-induced lysosome biogenesis is essential for the clearance of cytoplasmic DNA and the elimination of invading pathogens. Collectively, our findings underscore the induction of lysosome biogenesis as a novel function of the CGAS-STING1 pathway.Abbreviation: ATG: autophagy-related; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; GABARAP: GABA type A receptor-associated protein; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin kinase; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB.

01 Apr 2025·Leukemia

STAT6 mutations compensate for CREBBP mutations and hyperactivate IL4/STAT6/RRAGD/mTOR signaling in follicular lymphoma

Article

Author: Malek, Isabella A ; Bedi, Karan ; Shedden, Kerby ; Malek, Sami N ; Shao, Qiangqiang

AbstractActivating mutations in STAT6 are common in Follicular Lymphoma (FL) and transformed FL and various other B cell lymphomas. Here, we report RNA-seq based gene expression data on normal human lymph node derived B lymphocytes (NBC; N = 6), and primary human FL WT (N = 11) or mutant (N = 4) for STAT6 before and after ex vivo stimulation with IL4. We found that STAT6 mutants result in broad based augmentation of IL4-induced gene expression. Unexpectedly, in FL with WT STAT6 we measured reduced baseline and IL4-induced gene expression levels when compared with NBC lymphocytes or FL with STAT6 mutations. We tracked the attenuated IL4/JAK/STAT6 response to co-existing CREBBP mutations and experimentally verified that intact CREBBP is required for the induction of many IL4-induced genes. One of the IL4-induced genes here identified is RRAGD, a small G-protein involved in lysosomal mTOR activation. We show that IL4 treatment induced RRAGD expression, that RRAGD is required for mTOR activation in lymphoma cells and that IL4-enhanced BCR signaling induced mTOR activation. The IL4 and BCR-induced mTOR activation was reduced by CREBBP mutants and augmented by mutant STAT6, establishing a link between STAT6 mutations and mTOR regulated pro-growth pathways in lymphoma.

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RRAG

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