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Caspase-9 has two splice variants, pro-apoptotic caspase-9a and anti-apoptotic caspase-9b, which are regulated by RNA trans-factors associated with exon 3 of caspase-9 pre-mRNA (C9/E3). In this study, we identified hnRNP U as an RNA trans-factor associated with C9/E3. Down-regulation of hnRNP U led to a decrease in the caspase-9a/9b mRNA ratio, demonstrating a novel enhancing function. Importantly, hnRNP U bound specifically to C9/E3 at an RNA cis-element previously reported as the binding site for the splicing repressor, hnRNP L. Phosphorylated hnRNP L interfered with hnRNP U binding to C9/E3, and our results demonstrate the importance of the phosphoinositide 3-kinase/AKT pathway in modulating the association of hnRNP U to C9/E3. Taken together, these findings show that hnRNP U competes with hnRNP L for binding to C9/E3 to enhance the inclusion of the four-exon cassette, and this splice-enhancing function is blocked by the AKT pathway via phosphorylation of hnRNP L.
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http://dx.doi.org/10.1074/jbc.M112.443333 | DOI Listing |
Mol Genet Genomic Med
September 2025
Research Centre for Medical Genetics, Moscow, Russia.
Background: Developmental and epileptic encephalopathies (DEEs) comprise a diverse range of disorders that can arise from both genetic and non-genetic causes. Genetic DEEs are linked to pathogenic variants in various genes with different molecular functions. The wide clinical and genetic variability found in DEEs poses a considerable challenge for accurate diagnosis even with the use of comprehensive diagnostic approaches such as whole genome sequencing (WGS).
View Article and Find Full Text PDFSci Prog
September 2025
Department of Cardiology, Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, China.
ObjectiveType 1 myocardial infarction (T1MI) is primarily caused by the formation of coronary thrombi, which leads to acute myocardial ischemia and hypoxia and is associated with high morbidity and mortality rates. However, the effects of thrombus-derived exosomes (TEs) on endothelial cell function remain unclear. The aim of this study was to investigate the interaction between lncRNA LOC101928697, which is enriched in TEs, and FUS proteins, as well as their impact on endothelial cell function.
View Article and Find Full Text PDFGenes Chromosomes Cancer
August 2025
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
We present a case of a 51-year-old male with a pseudoglandular cellular schwannoma arising from the brachial plexus, which contains the expected molecular aberrations for a schwannoma (chromosome 22q loss encompassing the NF2 and LZTR1 genes) as well as a FUS::KLF17 rearrangement. Pseudoglandular schwannomas are rare morphologic variants of schwannomas that contain gland-like spaces lined by S100-positive, cytokeratin-negative pseudocolumnar Schwann cells. Fusions involving FUS and EWSR are commonly found in myoepithelial tumors of bone and soft tissue.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
Glioblastoma (GBM) is a highly aggressive brain tumour characterised by a poor prognosis and resistance to anti-angiogenic treatments. Vasculogenic mimicry (VM), in which tumour cells form vessel-like structures independent of endothelial cells, has emerged as a key mechanism hindering the efficacy of anti-angiogenic therapies. Recent research highlights the central role of RNA-binding proteins (RBPs) in regulating VM through diverse post-transcriptional mechanisms, including mRNA decay induction and translational repression.
View Article and Find Full Text PDFSci Adv
August 2025
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
The pseudouridine synthase DKC1 regulates internal ribosome entry site (IRES)-dependent translation and is up-regulated in cancers by the MYC family of oncogenes. The functional significance of DKC1 up-regulation and the mechanistic connection between pseudouridylation and IRES-mediated translation remain poorly understood. Here, we report that DKC1 drives an ATF4-mediated transcriptional program that supports amino acid metabolism and stress adaptation.
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