Gene expression is a complex process requiring many control mechanisms to achieve a desired phenotype. DNA accessibility within chromatin is well established as an important determinant of gene expression. By contrast, while mRNA also associates with a complement of proteins, the exact nature of messenger ribonucleoprotein (mRNP) packaging and its functional relevance is not as clear.
View Article and Find Full Text PDFAge-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy.
View Article and Find Full Text PDFPurpose Of Review: Currently, the most widely used treatment for endothelial disease is endothelial replacement via endothelial keratoplasty. Increasingly selective techniques have allowed for increased safety and faster visual recovery. However, alternative treatment options that are lower in cost, require less surgical expertise, and rely less on tissue availability are needed.
View Article and Find Full Text PDF-methyladenosine (mA) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive.
View Article and Find Full Text PDFRNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N -methyladenosine (m A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation.
View Article and Find Full Text PDFIn mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA-mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary gland cells, AGO1 associates with transcriptional enhancers of estrogen receptor α (ERα) and that this association is up-regulated by treating the cells with estrogen (E2), displaying a positive correlation with the activation of these enhancers.
View Article and Find Full Text PDFFTO, the first RNA demethylase discovered, mediates the demethylation of internal N-methyladenosine (mA) and N, 2-O-dimethyladenosine (mA) at the +1 position from the 5' cap in mRNA. Here we demonstrate that the cellular distribution of FTO is distinct among different cell lines, affecting the access of FTO to different RNA substrates. We find that FTO binds multiple RNA species, including mRNA, snRNA, and tRNA, and can demethylate internal mA and cap mA in mRNA, internal mA in U6 RNA, internal and cap mA in snRNAs, and N-methyladenosine (mA) in tRNA.
View Article and Find Full Text PDFVarious factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation "gradient" is thought to result from preferential binding of the H3K4 methyltransferase Set1/complex associated with Set1 (COMPASS) to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1.
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