Natural antisense transcripts as versatile regulators of gene expression

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Апрель 17, 2024

Язык: Английский

---

Multifaceted roles of RNA editing enzyme ADAR1 in innate immunity

RNA, Год журнала: 2024, Номер 30(5), С. 500 - 511

Опубликована: Март 26, 2024

Innate immunity must be tightly regulated to enable sensitive pathogen detection while averting autoimmunity triggered by pathogen-like host molecules. A hallmark of viral infection, double-stranded RNAs (dsRNAs) are also abundantly encoded in mammalian genomes, necessitating surveillance mechanisms distinguish “self” from “nonself.” ADAR1, an RNA editing enzyme, has emerged as essential safeguard against dsRNA-induced autoimmunity. By converting adenosines inosines (A-to-I) long dsRNAs, ADAR1 covalently marks endogenous thereby blocking the activation cytoplasmic dsRNA sensor MDA5. Moreover, beyond its function, binding impedes innate immune sensors PKR and ZBP1. Recent landmark studies underscore utility silencing for cancer immunotherapy, exploiting ADAR1-dependence developed certain tumors unleash antitumor response. In this perspective, we summarize genetic mechanistic evidence ADAR1's multipronged role suppressing dsRNA-mediated explore evolving roles immuno-oncology target.

Язык: Английский

---

RNA editing and immune control: from mechanism to therapy

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 86, С. 102195 - 102195

Опубликована: Апрель 21, 2024

Язык: Английский

---

IRE1α silences dsRNA to prevent taxane-induced pyroptosis in triple-negative breast cancer

Cell, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

---

Obstacles in quantifying A-to-I RNA editing by Sanger sequencing

Methods in enzymology on CD-ROM/Methods in enzymology, Год журнала: 2025, Номер unknown, С. 285 - 302

Опубликована: Янв. 1, 2025

Язык: Английский

---

Spontaneous base flipping helps drive Nsp15’s preferences in double stranded RNA substrates

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 4, 2025

Abstract Coronaviruses evade detection by the host immune system with help of endoribonuclease Nsp15, which regulates levels viral double stranded RNA cleaving 3′ uridine (U). While prior structural data shows that to cleave RNA, Nsp15’s target U must be flipped out helix, it is not yet understood whether Nsp15 initiates flipping or captures spontaneously bases. We address this gap designing fluorinated substrates allow us directly relate a U’s sequence context both its tendency flip and susceptibility cleavage Nsp15. Through combination nuclease assays, 19 F NMR spectroscopy, mass spectrometry, single particle cryo-EM, we determine acts most efficiently on unpaired Us, particularly those are already flipped. Across contexts, find efficiency related flip. Overall, our findings unify previous characterizations preferences, suggest activity during infection partially driven bulged otherwise relatively accessible Us appear at strategic positions in RNA.

Язык: Английский

---

Harnessing double-stranded RNA (dsRNA): a sustainable approach to pest management

Physiology and Molecular Biology of Plants, Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

Язык: Английский

---

Circular RNA circCLASP2 promotes nasopharyngeal carcinoma progression through binding to DHX9 to enhance PCMT1 translation

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 6, 2025

Circular RNAs (circRNAs), characterized by their covalently closed-loop structures, constitute a distinct class of non-coding RNAs. They play pivotal regulatory roles within cells and are intricately associated with the progression malignant tumors. However, underlying mechanisms in nasopharyngeal carcinoma (NPC) have yet to be fully uncovered comprehensively understood. Employing RNA sequencing technology, high-abundance circular NPC were identified. Expression analysis circCLASP2 tissues was conducted using quantitative real-time polymerase chain reaction (qRT-PCR) situ hybridization experiments. Through vitro vivo functional assays, influence on proliferation metastasis investigated. LC-MS/MS technology analyzed binding partners circCLASP2, its differentially regulated targets, proteins PCMT1. Interactions among DHX9 protein, PCMT1 mRNA elucidated through immunoprecipitation pull-down techniques. The effects G-quadruplex (rG4) structures translation explored immunofluorescence (IF), ribosomal gradient separation, dual-luciferase reporter assays. Immunoprecipitation (IP) revealed downstream effector circCLASP2-DHX9-PCMT1 axis Phalloidin staining confirmed ultimate effect cytoskeleton. PDS treatment applied for interventions NPC, demonstrating potential therapeutic avenues. Our research that novel circRNA has not been reported tumors, is upregulated fosters cell both vivo. Mechanistically, acts as molecular scaffold, facilitating approximation mRNA. unwinds inhibitory rG4 structure near initiation site mRNA, increasing expression. binds upregulates cytoskeleton-associated proteins, modulating cytoskeleton strength dynamics ultimately driving metastasis. In experiments, significantly inhibits growth metastasis, showcasing promising potential. investigation pinpointed RNA, which augments cytoskeletal functions via DHX9-PCMT1 axis, contributing malignancy NPC. This pathway holds promise target Furthermore, these molecules could also serve biomarkers adjunct diagnosis prognosis assessment

Язык: Английский

---

Cellular dsRNA interactome captured by K1 antibody reveals the regulatory map of exogenous RNA sensing

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 7, 2025

RNA-binding proteins (RBPs) provide a critical post-transcriptional regulatory layer in determining RNA fate. Currently, UV crosslinking followed by oligo-dT pull-down is the gold standard identifying RBP repertoire of poly-adenylated RNAs, but such method ineffective capturing RBPs that recognize double-stranded RNAs (dsRNAs). Here, we utilize anti-dsRNA K1 antibody immunoprecipitation quantitative mass spectrometry to comprehensively identify bound cellular dsRNAs without external stimulus. Notably, our dsRNA interactome contains involved sensing N6-methyladenosine and stress granule components. We further perform targeted CRISPR-Cas9 knockout functional screening discover can regulate interferon (IFN) response during exogenous sensing. Interestingly, most dsRBPs promote IFN-β secretion stimulation act as antiviral factors HCoV-OC43 infection. Our capture provides an unbiased comprehensive characterization putative will facilitate understanding physiological pathological contexts. Exploration using studies these dsRBP candidates elucidate role immune responses their importance viral

Язык: Английский

---

PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 8, 2025

Abstract The innate immune sensor PKR for double-stranded RNA (dsRNA) is critical antiviral defense, but its aberrant activation by cellular dsRNA linked to various diseases. dsRNA-binding protein PACT plays a yet controversial role in this pathway. We show that directly suppresses endogenous ligands, such as inverted-repeat Alu RNAs, which robustly activate the absence of PACT. Instead competing binding, prevents from scanning along dsRNA—a necessary step molecules encounter and phosphorylate each other activation. While favors longer increased co-occupancy scanning-mediated activation, also more susceptible PACT-mediated regulation due PACT-PKR co-occupancy. Unlike viral inhibitors constitutively suppress PKR, RNA-dependent mechanism allows fine-tune based on length quantity, ensuring self-tolerance without sequestering most dsRNA.

Язык: Английский

---