MicroRNAs (miRNAs) are important regulators of genes expression. Their levels are precisely controlled through modulating the activity of the microprocesser complex (MC). Here, we report that JANUS, a homology of the conserved U2 snRNP assembly factor in yeast and human, is required for miRNA accumulation. JANUS associates with MC components Dicer-like 1 (DCL1) and SERRATE (SE) and directly binds the stem-loop of pri-miRNAs. In a hypomorphic janus mutant, the activity of DCL1, the numbers of MC, and the interaction of primary miRNA transcript (pri-miRNAs) with MC are reduced. These data suggest that JANUS promotes the assembly and activity of MC through its interaction with MC and/or pri-miRNAs. In addition, JANUS modulates the transcription of some pri-miRNAs as it binds the promoter of pri-miRNAs and facilitates Pol II occupancy of at their promoters. Moreover, global splicing defects are detected in janus. Taken together, our study reveals a novel role of a conserved splicing factor in miRNA biogenesis.
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http://dx.doi.org/10.1093/nar/gkad1105 | DOI Listing |
J Med Chem
January 2025
Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610064, China.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, and the need for effective systemic therapies for HCC is urgent. Our previous work reveals that Pin1 is a potential anti-HCC target, which regulates miRNA biogenesis and identifies as a novel Pin1 inhibitor to suppresses HCC. However, a great demand in HCC therapy as well as the limited chemical stability and pharmacokinetic feature of motivated us to find improved Pin1 inhibitors.
View Article and Find Full Text PDFCytotechnology
April 2025
Department of Critical Care Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), No. 1017, North Dongmen Road, Luohu District, Shenzhen, 518020 Guangdong China.
This study aimed to investigate the role of circular RNAs (circRNAs) in sepsis-induced acute gastrointestinal injury (AGI), focusing on their potential as biomarkers and their involvement in disease progression. Peripheral blood samples from 14 patients with sepsis-induced AGI and healthy volunteers were collected. RNA sequencing was performed to profile circRNA and miRNA expression.
View Article and Find Full Text PDFVet Clin Pathol
January 2025
Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
MicroRNAs (miRNAs or miRs) are small, non-coding RNAs that play a crucial role in gene regulation, making them potential biomarkers for various diseases. In the field of veterinary medicine, there is a growing interest in exploring the diagnostic and therapeutic potential of miRNAs in kidney diseases affecting dogs and cats. This review focuses on the use of urinary miRNAs as biomarkers for chronic kidney disease (CKD) in these companion animals.
View Article and Find Full Text PDFTrends Genet
January 2025
Institute for Computational Genomic Medicine, Goethe University Frankfurt, Frankfurt, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Frankfurt, Germany. Electronic address:
MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, SAR, China.
Background: Sclerostin (SOST) is traditionally regarded as an osteocyte-derived secreted glycoprotein that regulates bone mineralization. Recent studies reported that SOST is also released from non-skeletal sources, especially during inflammation. However, the cellular source and regulatory mechanisms governing SOST generation in inflammation remain unclear.
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