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Nat Chem
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Published: March 2025
Biomolecular condensates composed of proteins and RNA are one approach by which cells regulate post-transcriptional gene expression. Their formation typically involves the phase separation of intrinsically disordered proteins with a target mRNA, sequestering the mRNA into a liquid condensate. This sequestration regulates gene expression by modulating translation or facilitating RNA processing. Here we engineer synthetic condensates using a fusion of an RNA-binding protein, the human Pumilio2 homology domain (Pum2), and a synthetic intrinsically disordered protein, an elastin-like polypeptide (ELP), that can bind and sequester a target mRNA transcript. In protocells, sequestration of a target mRNA largely limits its translation. Conversely, in Escherichia coli, sequestration of the same target mRNA increases its translation. We characterize the Pum2-ELP condensate system using microscopy, biophysical and biochemical assays, and RNA sequencing. This approach enables the modulation of cell function via the formation of synthetic biomolecular condensates that regulate the expression of a target protein.
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http://dx.doi.org/10.1038/s41557-024-01706-7 | DOI Listing |
G protein-coupled receptor, class C, group 5, member D (GPRC5D) has emerged as a novel target for chimeric antigen receptor (CAR) T-cell therapy, demonstrating promising efficacy in multiple myeloma (MM). However, disease relapse is still common, and the mechanism of resistance remains poorly understood. In this study, we conducted whole-genome sequencing (WGS) and whole-genome bisulfite sequencing (WGBS) on MM samples from 10 patients who relapsed after GPRC5D CAR T-cell therapy.
View Article and Find Full Text PDFCell Death Discov
March 2025
Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Fuchs endothelial corneal dystrophy (FECD) is the leading cause of vision-threatening corneal endothelial dystrophy without pharmacologic treatments. Corneal endothelial-mesenchymal transition (cEndMT), a specific cellular phenotypic transition, is implicated in the vicious cycle in FECD pathogenesis. Here, we investigated the reversible epigenetic regulation of N-methyladenosine (mA) during cEndMT process and FECD progression.
View Article and Find Full Text PDFNat Commun
March 2025
Institut de Biologie Valrose, Université Côte d'Azur, CNRS, Inserm, Nice, France.
Localization of mRNAs to neuronal terminals, coupled to local translation, has emerged as a prevalent mechanism controlling the synaptic proteome. However, the physiological regulation and function of this process in the context of mature in vivo memory circuits has remained unclear. Here, we combined synaptosome RNA profiling with whole brain high-resolution imaging to uncover mRNAs with different localization patterns in the axons of Drosophila Mushroom Body memory neurons, some exhibiting regionalized, input-dependent, recruitment along axons.
View Article and Find Full Text PDFAnn Clin Lab Sci
January 2025
Department of Endocrinology, Peking University, Shenzhen, Guangdong, China.
Objective: Chronic diabetic nephropathy (CDN) is one of the common complications of the chronic diabetes. The FGF23/FGFR3-mediated signaling pathway is involved in CDN. Whether miR-190a-3P participates in CDN through regulation of FGFR3 remains to be elucidated.
View Article and Find Full Text PDFAnn Clin Lab Sci
January 2025
Department of General Surgery, The Second People's Hospital of China Three Gorges University, Yichang, Hubei, China
Objective: We explored the mechanism of action of microRNA-146a in the lung cancer cell line A549 through the Noth1/Hes-1 signal pathway.
Methods: A549 cells were divided into a control NT group without transfection, NC group with transfection of miR-146a-NC, and MM group with transfection of miR-146a mimics. We employed qRT-PCR, MTT, Hoechst33258 fluorescence staining, Transwell assay, cell wound scratch assay, and Western blot for detection of the expression of miR-146a and Notch1/Hes-1, cell activity, apoptotic capacity, and invasion and migration abilities.
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