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000280948 0247_ $$2doi$$a10.1016/j.celrep.2025.115735
000280948 0247_ $$2pmid$$apmid:40402745
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000280948 037__ $$aDZNE-2025-01030
000280948 041__ $$aEnglish
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000280948 1001_ $$aMadej, Magdalena$$b0
000280948 245__ $$aPUS10-induced tRNA fragmentation impacts retrotransposon-driven inflammation.
000280948 260__ $$aMaryland Heights, MO$$bCell Press$$c2025
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000280948 520__ $$aPseudouridine synthases (PUSs) catalyze the isomerization of uridine (U)-to-pseudouridine (Ψ) and have emerging roles in development and disease. How PUSs adapt gene expression under stress remains mostly unexplored. We identify an unconventional role for the Ψ 'writer' PUS10 impacting intracellular innate immunity. Using Pus10 knockout mice, we uncover cell-intrinsic upregulation of interferon (IFN) signaling, conferring resistance to inflammation in vivo. Pus10 loss alters tRNA-derived small RNAs (tdRs) abundance, perturbing translation and endogenous retroelements expression. These alterations promote proinflammatory RNA-DNA hybrids accumulation, potentially activating cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING). Supplementation with selected tdR pools partly rescues these effects through interactions with RNA processing factors that modulate immune responses, revealing a regulatory circuit that counteracts cell-intrinsic inflammation. By extension, we define a PUS10-specific molecular fingerprint linking its dysregulation to human autoimmune disorders, including inflammatory bowel diseases. Collectively, these findings establish PUS10 as a viral mimicry modulator, with broad implications for innate immune homeostasis and autoimmunity.
000280948 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000280948 650_7 $$2Other$$aCP: Molecular biology
000280948 650_7 $$2Other$$aPUS10
000280948 650_7 $$2Other$$aRNA-DNA hybrids
000280948 650_7 $$2Other$$acGAS-STING
000280948 650_7 $$2Other$$ahematopoietic stem cell
000280948 650_7 $$2Other$$ainflammation
000280948 650_7 $$2Other$$ainflammatory bowel disease
000280948 650_7 $$2Other$$ainterferon
000280948 650_7 $$2Other$$apseudouridine
000280948 650_7 $$2Other$$atRNA-derived small RNAs
000280948 650_7 $$2Other$$atransposable elements
000280948 650_7 $$2Other$$aviral mimicry
000280948 650_7 $$2NLM Chemicals$$aRetroelements
000280948 650_7 $$09014-25-9$$2NLM Chemicals$$aRNA, Transfer
000280948 650_7 $$0EC 5.4.99.-$$2NLM Chemicals$$apseudouridine synthases
000280948 650_7 $$0EC 5.4.-$$2NLM Chemicals$$aIntramolecular Transferases
000280948 650_7 $$0EC 4.2.1.-$$2NLM Chemicals$$aHydro-Lyases
000280948 650_7 $$09008-11-1$$2NLM Chemicals$$aInterferons
000280948 650_7 $$2NLM Chemicals$$aMembrane Proteins
000280948 650_2 $$2MeSH$$aAnimals
000280948 650_2 $$2MeSH$$aRetroelements: genetics
000280948 650_2 $$2MeSH$$aInflammation: genetics
000280948 650_2 $$2MeSH$$aInflammation: pathology
000280948 650_2 $$2MeSH$$aInflammation: metabolism
000280948 650_2 $$2MeSH$$aMice
000280948 650_2 $$2MeSH$$aRNA, Transfer: metabolism
000280948 650_2 $$2MeSH$$aRNA, Transfer: genetics
000280948 650_2 $$2MeSH$$aMice, Knockout
000280948 650_2 $$2MeSH$$aHumans
000280948 650_2 $$2MeSH$$aImmunity, Innate
000280948 650_2 $$2MeSH$$aIntramolecular Transferases: metabolism
000280948 650_2 $$2MeSH$$aIntramolecular Transferases: genetics
000280948 650_2 $$2MeSH$$aMice, Inbred C57BL
000280948 650_2 $$2MeSH$$aHydro-Lyases: metabolism
000280948 650_2 $$2MeSH$$aHydro-Lyases: genetics
000280948 650_2 $$2MeSH$$aInterferons: metabolism
000280948 650_2 $$2MeSH$$aSignal Transduction
000280948 650_2 $$2MeSH$$aMembrane Proteins: metabolism
000280948 7001_ $$aNgoc, Phuong Cao Thi$$b1
000280948 7001_ $$aMuthukumar, Sowndarya$$b2
000280948 7001_ $$aKonturek-Cieśla, Anna$$b3
000280948 7001_ $$aTucciarone, Silvia$$b4
000280948 7001_ $$aGermanos, Alexandre$$b5
000280948 7001_ $$aAshworth, Christian$$b6
000280948 7001_ $$aKotarsky, Knut$$b7
000280948 7001_ $$aGhosh, Sudip$$b8
000280948 7001_ $$aFan, Zhimeng$$b9
000280948 7001_ $$aFritz, Helena$$b10
000280948 7001_ $$aPascual-Gonzalez, Izei$$b11
000280948 7001_ $$aHuerta, Alain$$b12
000280948 7001_ $$aGuzzi, Nicola$$b13
000280948 7001_ $$aColazzo, Anita$$b14
000280948 7001_ $$aBeneventi, Giulia$$b15
000280948 7001_ $$0P:(DE-2719)2814197$$aLee, Hang-mao$$b16
000280948 7001_ $$aCieśla, Maciej$$b17
000280948 7001_ $$aDouse, Christopher$$b18
000280948 7001_ $$aKato, Hiroki$$b19
000280948 7001_ $$aSwaminathan, Vinay$$b20
000280948 7001_ $$aAgace, William W$$b21
000280948 7001_ $$aCastellanos-Rubio, Ainara$$b22
000280948 7001_ $$0P:(DE-2719)2811779$$aSalomoni, Paolo$$b23$$udzne
000280948 7001_ $$aBryder, David$$b24
000280948 7001_ $$aBellodi, Cristian$$b25
000280948 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2025.115735$$gVol. 44, no. 6, p. 115735 -$$n6$$p115735$$tCell reports$$v44$$x2211-1247$$y2025
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