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MicroRNAs (miRNAs) play an essential role in plant growth and development, and as such, their biogenesis is fine-tuned via regulation of the core microprocessor components. Here, we report that AAR2, a homolog of a U5 snRNP assembly factor in yeast and humans, not only acts in splicing but also promotes miRNA biogenesis. AAR2 interacts with the microprocessor component hyponastic leaves 1 (HYL1) in the cytoplasm, nucleus, and dicing bodies. In mutants, abundance of nonphosphorylated HYL1, the active form of HYL1, and the number of HYL1-labeled dicing bodies are reduced. Primary miRNA (pri-miRNA) accumulation is compromised despite normal promoter activities of genes in mutants. RNA decay assays show that the mutation leads to faster degradation of pri-miRNAs in a HYL1-dependent manner, which reveals a previously unknown and negative role of HYL1 in miRNA biogenesis. Taken together, our findings reveal a dual role of AAR2 in miRNA biogenesis and pre-messenger RNA splicing.
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http://dx.doi.org/10.1073/pnas.2208415119 | DOI Listing |
Alzheimers Dement
September 2025
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Introduction: Mutations in SORL1, encoding the sorting receptor Sortilin-related receptor with A-type repeats (SORLA), are found in individuals with Alzheimer's disease (AD). We studied SORLA, carrying a mutation in its ligand binding domain, to learn more about receptor functions relevant for human brain health.
Methods: We investigated consequences of SORLA expression in induced pluripotent stem cell (iPSC)-derived human neurons and microglia, using unbiased proteome screens and functional cell assays.
Cell Signal
September 2025
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Respiratory Immunology research center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. 2.48 million new cases were reported globally in 2022, driven by rising adenocarcinoma rates linked to environmental factors such as air pollution.
View Article and Find Full Text PDFWIREs Mech Dis
September 2025
GIMUNICAH, Faculty of Medicine, Pontificia Universidad Católica de Honduras, San Pedro Sula, Honduras.
The nucleolus, traditionally known for its role in ribosome biogenesis, is now recognized for its broader functions, including cellular stress adaptation and its involvement in various pathological processes, such as ribosomal alterations, viral infections, autoimmune disorders, and age-related diseases. Disruptions in nucleolar function can impair protein synthesis, cellular homeostasis, and immune responses, leading to multisystem disorders and increased susceptibility to neoplasms. This review classifies nucleolus-associated diseases into seven categories: deficiencies in protein synthesis, ribosomal and non-ribosomal alterations, cancer and nucleolar alterations, diseases related to aging and cellular stress, autoimmune diseases, and viral diseases.
View Article and Find Full Text PDFAm J Reprod Immunol
September 2025
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Objective: Exosomes are secreted by most cell types and reflect the internal state of their cells of origin, playing crucial roles in the progression of various pathological conditions. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue outside the uterus, including in the ovaries, fallopian tubes, and peritoneal cavity. It primarily affects women of reproductive age and is often associated with infertility.
View Article and Find Full Text PDFJ Transl Med
September 2025
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
PIP5K1α is a key member of the lipid kinase family, involved in several cellular processes including cell proliferation and differentiation, cytoskeletal remodeling, inositol-phospholipid signaling, intracellular vesicle transport, and protein secretion. Emerging evidence now highlights critical functions of PIP5K1α in asthma-related biological processes. In this review, we aim to consolidate existing literature on the involvement of PIP5K1α in asthma pathogenesis.
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