TRAF1 is a member of the TRAF family, which plays important roles in signal transduction that mediate cell life and death in the immune response, inflammatory and malignant diseases. It is known that TRAF1 transcription is inducible by various cytokines, but little is known about the regulation of its mRNA translation. In the present study, we demonstrated that the human TRAF1 mRNA has an unusually long 5'-UTR that contains internal ribosome entry segment (IRES) regulating its translation. By performing gene transfection and reporter assays, we revealed that this IRES sequence is located within the 572 nt upstream from the AUG start codon. An element between nt -392 and -322 was essential for the IRES activity. Interestingly, we found that the TRAF1 expression is induced in cancer cells by chemotherapeutic drug vincristine that regulates cytoplasmic localization of polypyrimidine tract binding protein, which may contribute to the IRES-dependent translation of TRAF1 during vincristine treatment. These results indicate that TRAF1 translation is initiated via the IRES and regulated by vincristine, and suggest that regulation of the IRES-dependent translation of TRAF1 may be involved in effecting the cancer cell response to vincristine treatment.
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http://dx.doi.org/10.1093/nar/gkq183 | DOI Listing |
Biochem Biophys Res Commun
November 2024
The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
The imbalance of vascular endothelial cell homeostasis is the key mechanism for the progression of many vascular diseases. RNA modification, particularly N-Methyladenosine (mA), plays important function in numerous biological processes. Nevertheless, the regulatory function of mA RNA methylation in endothelial dysfunction remains insufficiently characterized.
View Article and Find Full Text PDFPeerJ
July 2024
Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of breast cancer is characterized by high cancer cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to the malignant process of cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC.
View Article and Find Full Text PDFBMC Med Genomics
July 2024
Department of Pediatrics, Clinical and Translational Research Center, University at Buffalo Jacobs School of Medicine School Medicine & Biomedical Sciences, 701 Ellicott St, Buffalo, NY, 14203, USA.
Background: Although genome-wide association studies (GWAS) have identified multiple regions conferring genetic risk for juvenile idiopathic arthritis (JIA), we are still faced with the task of identifying the single nucleotide polymorphisms (SNPs) on the disease haplotypes that exert the biological effects that confer risk. Until we identify the risk-driving variants, identifying the genes influenced by these variants, and therefore translating genetic information to improved clinical care, will remain an insurmountable task. We used a function-based approach for identifying causal variant candidates and the target genes on JIA risk haplotypes.
View Article and Find Full Text PDFBiochem Cell Biol
August 2023
Key Laboratory of Pathobiology, Ministry of Education, and Department of pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Epigenetic regulation contributes to human health and disease, especially cancer, but the mechanisms of many epigenetic regulators remain obscure. Most research is focused on gene regulatory processes, such as mRNA translation and DNA damage repair, rather than the effects on biological functions like mitochondrial activity and oxidative phosphorylation. Here, we identified an essential role for the histone chaperone structure-specific recognition protein 1 (SSRP1) in mitochondrial oxidative respiration in hepatocellular carcinoma, and found that SSRP1 suppression led to mitochondrial damage and decreased oxidative respiration.
View Article and Find Full Text PDFBMC Genomics
March 2023
Center for Genetic Epidemiology and Genomics, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu, 215123, People's Republic of China.
Background: RNA modification plays important roles in many biological processes, such as gene expression control. The aim of this study was to identify single nucleotide polymorphisms related to RNA modification (RNAm-SNPs) for rheumatoid arthritis (RA) as putative functional variants.
Methods: We examined the association of RNAm-SNPs with RA in summary data from a genome-wide association study of 19,234 RA cases and 61,565 controls.
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