The DNA binding architectural protein, TCF, and the transcriptional activator, beta-catenin, form a complex that regulates the expression of diverse target genes during early development and carcinogenesis. As an approach to modulating transcription by this complex, we selected an RNA aptamer that binds to the DNA binding domain of TCF-1. The aptamer interfered with the binding of TCF-1 to its specific DNA recognition sequences in vitro and also inhibited DNA binding of cellular TCF-1. We also developed the truncated version of the aptamer for efficient delivery to the cells. Structural analysis of the truncated aptamer revealed that a stem-loop with an internal loop was responsible for the binding to TCF-1. Similar approach may well be applicable to other proteins, especially DNA binding transcription factors, in order to modulate their DNA binding and transcriptional activity in the cells.
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http://dx.doi.org/10.1016/j.bbrc.2005.02.119 | DOI Listing |
Mol Ther Nucleic Acids
March 2025
Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czechia.
Impaired fibroblast growth factor receptor (FGFR) signaling is associated with many human conditions, including growth disorders, degenerative diseases, and cancer. Current FGFR therapeutics are based on chemical inhibitors of FGFR tyrosine kinase activity (TKIs). However, FGFR TKIs are limited in their target specificity as they generally inhibit all FGFRs and other receptor tyrosine kinases.
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March 2025
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.
Preeclampsia (PE) is a significant complication of pregnancy, occurring in approximately 10% of pregnancies. However, the underlying mechanisms of this condition remain unclear. Placentation and tumorigenesis both share many characteristics, but PE is the result of insufficient placentation, in contrast to the overaggression of tumorigenesis.
View Article and Find Full Text PDFBioinform Adv
December 2024
Digital Technologies Research Center, National Research Council Canada, Ottawa, ON, K1A 0R6, Canada.
Motivation: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is a ground-breaking genome editing tool, which has revolutionized cell and gene therapies. One of the essential components involved in this system that ensures its success is the design of an optimal single-guide RNA (sgRNA) with high on-target cleavage efficiency and low off-target effects. This is challenging as many conditions need to be considered, and empirically testing every design is time-consuming and costly.
View Article and Find Full Text PDFACS Omega
December 2024
Department of Urology, Suzhou Ninth Hospital affiliated to Soochow University, Suzhou 215000, China.
Cis-regulatory elements bridge enhancers and gene promoters to control gene expression via distal DNA interaction and three-dimensional chromosomal conformation organization. The aberrant changes of cis-acting regulatory systems as one type of the epigenetic regulative ways may be connected with human genetic diseases. Klotho, as an antiaging protein, is selectively expressed in kidney tissues and plays a crucial role in preventing chronic kidney disease (CKD) and renal fibrosis.
View Article and Find Full Text PDFHeliyon
January 2025
Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education, Guangxi Key Laboratory of Landscape Resources Conservation and Sustainable Utilization in Lijiang River Basin (Guangxi Normal University), University Engineering Research Center of Bioinformation and Genetic Improvement of Specialty Crops, Guangxi, Guilin, Guangxi, 541006, China.
Our previous study found that WRINKLED1-like (DpWRI1-like) was a key regulatory factor of lipid biosynthesis in . gene and target genes of DpWRI1-like have been obtained in our previous study, but the interacting proteins of DpWRI1-like are unclear now, which has limited a deep understanding of the function of DpWRI1-like. Yeast two-hybrid was widely used to identify protein-protein interaction.
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