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Structural basis of 5' splice site recognition by the minor spliceosome.
Mol Cell
January 2025
European Molecular Biology Laboratory (EMBL), EMBL Grenoble, 71 Avenue des Martyrs, 38042 Grenoble, France. Electronic address:
The minor spliceosome catalyzes excision of U12-dependent introns from precursors of eukaryotic messenger RNAs (pre-mRNAs). This process is critical for many cellular functions, but the underlying molecular mechanisms remain elusive. Here, we report a cryoelectron microscopy (cryo-EM) reconstruction of the 13-subunit human U11 small nuclear ribonucleoprotein particle (snRNP) complex in apo and substrate-bound forms, revealing the architecture of the U11 small nuclear RNA (snRNA), five minor spliceosome-specific factors, and the mechanism of the U12-type 5' splice site (5'SS) recognition.
View Article and Find Full Text PDFA cardiac transcriptional enhancer is repurposed during regeneration to activate an anti-proliferative program.
Development
January 2025
Department of Biological Chemistry and Pharmacology, The Ohio State University Medical Center, Columbus OH, USA.
Zebrafish have a high capacity to regenerate their hearts. Several studies have surveyed transcriptional enhancers to understand how gene expression is controlled during heart regeneration. We have identified REN or the runx1 enhancer that during regeneration regulates the expression of the nearby runx1 gene.
View Article and Find Full Text PDFCamk2n1 deficiency reduces the NaCl cotransporter activity through the CUL3/KLHL3/WNK4 complex in the kidney.
Eur J Pharmacol
January 2025
Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Calcium/calmodulin dependent protein kinase II inhibitor 1 (Camk2n1) is closely associated with a peak logarithm of odds score in quantitative trait loci for systolic blood pressure. Increased Camk2n1 mRNA expression has been specifically observed in the kidneys of hypertension mouse models. However, the precise role of Camk2n1 in the kidney remains unclear.
View Article and Find Full Text PDFThe Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion.
Int J Mol Sci
December 2024
Department of Anatomy, Cellular and Molecular Research Group, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-625 00 Brno, Czech Republic.
CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion.
View Article and Find Full Text PDFOral Delivery of miR146a Conjugated to Cerium Oxide Nanoparticles Improves an Established T Cell-Mediated Experimental Colitis in Mice.
Pharmaceutics
December 2024
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children's at Diamond Children's Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA.
Dysregulated inflammation and oxidative stress are strongly implicated in the pathogenesis of inflammatory bowel disease. We have developed a novel therapeutic that targets inflammation and oxidative stress. It is comprised of microRNA-146a (miR146a)-loaded cerium oxide nanoparticles (CNPs) (CNP-miR146a).
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