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The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1 mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway.
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http://dx.doi.org/10.1073/pnas.2116757119 | DOI Listing |
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.
View Article and Find Full Text PDFJ Transl Med
August 2025
Department of Pharmacy, Yiyang Medical College, Yiyang, 413000, China.
Background: DDX27, a member of the DEAD-box RNA helicase family, plays a pivotal role in RNA metabolism and is essential for diverse cellular processes, including transcription, pre-mRNA splicing, translation, and ribosome biogenesis. Recent findings have implicated DDX27 as a substantial contributor to tumorigenesis and cancer progression across various malignancies, establishing its significance as a molecular hub that interacts with key oncogenic partners such as major vault protein (MVP) and nucleophosmin 1 (NPM1).
Methods: We conducted systematic search in the following comprehensive academic databases: PubMed, MEDLINE or Web of Science.