🧬 PubMed RNA Editing Daily Digest

Pentatricopeptide repeat (PPR) proteins, one of the largest families of RNA-binding proteins in higher plants, play essential roles in the post-transcriptional regulation of RNA metabolism in organelles. PPR proteins are predominantly localized in mitochondria and/or chloroplasts, and participate in various post-transcriptional processes, including RNA editing (C-to-U conversion), intron splicing, RNA stabilization, cleavage, and translation. Although the importance of PPR proteins in organellar biogenesis and plant development are well established, recent studies have revealed their critical roles in plant's response to biotic and abiotic stresses. In this review, recent advances in understanding how distinct subclasses of P- and PLS-class PPR proteins mediate organellar RNA metabolism and influence stress signaling networks in plant's response to biotic and abiotic stresses are summarized. In particular, this review focuses on their functional relevance in responses to drought, salinity, extreme temperatures, heavy metal stress response, as well as pathogen infection, with emphasis on mechanisms involving reactive oxygen species homeostasis and organelle-to-nucleus retrograde signaling. Furthermore, recent progress in the synthetic redesign of PPR motifs, which enables programmable RNA recognition, is discussed. These advances provide valuable insights into the regulatory roles of PPR proteins and highlight the potential applications of synthetic PPR systems as tools to improve plant performance and resilience to environmental stress in changing climate conditions.

Adenosine deaminase acting on RNA 1 (ADAR1) is a central regulator of innate immunity. By binding to and catalyzing adenosine-to-inosine deamination within double-stranded RNAs, ADAR1 mitigates the immunogenicity of self-derived RNAs and preserves cellular homeostasis. In this review, we summarize recent structural and mechanistic advances that illuminate key features of ADAR1 architecture, including how its multi-domains engage dsRNA substrates and contribute to substrate selectivity. Integrated with decades of biochemical and genetic studies, these insights refine our understanding of ADAR1's catalytic mechanism, domain-specific activities, and roles in suppressing immune signaling. We further highlight emerging knowledge on ADAR1's RNA substrate landscape, its interactions with protein partners, and the mechanistic principles that underlie its broad RNA editing and immune regulatory functions, with implications for disease pathogenesis and therapeutic RNA editing.

Immune checkpoint blockade (ICB) therapy continues to face limitations due to tumor resistance linked to suppressed interferon (IFN) signaling. This suppression can be attributed to multiple mechanisms, among which viral pathogens represent a compelling though not yet fully elucidated factor. Here, we demonstrate that exogenous Epstein-Barr virus-encoded EBNA1 drives immunosuppression via enhanced RNA-editing enzyme ADAR1-mediated RNA editing. Comparative tumor model analyses revealed that EBNA1 overexpression reduced CD8

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have transformed genome editing through unprecedented precision, and next-generation variants (base and prime editors) further enhance specificity by enabling targeted nucleotide changes without introducing double-strand DNA breaks. These technologies have unlocked broad applications in therapeutic gene correction, functional genomics, infectious disease management, diagnostics, agricultural engineering, environmental biotechnology, and synthetic biology. However, the targeted delivery of these systems remains a major challenge due to the large and chemically distinct nature of their components, including Cas protein or its base/prime editor fusions, guide RNA, and in some cases, DNA repair templates-which complicate packaging, stability, and cellular uptake. Additional hurdles arise from tissue and cell-type specificity, differential intracellular environments, variable editing efficiencies, and the persistent risk of off-target genome modifications. This review outlines the key challenges in the delivery of CRISPR technologies as well provides a comprehensive overview of both current and emerging delivery strategies, including viral vectors (adenovirus, adeno-associated virus, and lentivirus), non-viral physical approaches (microinjection, electroporation, ultrasound, and hydrodynamic tail-vein injection), and nanoparticle-based modalities (lipid and polymeric nanoparticles, gold nanoparticles, DNA nanostructures, and extracellular vesicles). We also discussed the diverse applications of CRISPR-Cas9 in gene therapy, immune cell engineering for cancer therapies, and agricultural innovation.

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, death. The global incidence of AD is projected to increase significantly, with late-onset AD being predominantly sporadic in nature. Over the past three decades, the Apolipoprotein E (APOE) gene has been recognized as the most important single genetic determinant of sporadic AD risk. The APOE4 allele is a major risk factor for AD and is known to exacerbate the pathological process for AD. Identifying protective variants that may reduce the risk or delay the onset of AD is of great significance for the development of effective treatments. This review comprehensively examines the protective effects of APOE and its related protective mutations. It also explores the impact of these unique protective variants at the cellular level during the pathological progression of AD. Furthermore, the review compiles new insights for AD treatment offered by these protective mutations, exploring the potential applications of APOE and its related protective variants in advanced therapeutic strategies, including gene editing, RNA editing, and stem cell therapy.