Half life blue shift mouse lock4/12/2023 ![]() No significant difference in 8OHdG/8OHG staining intensity between control and rd10 mouse retinas was observed. Furthermore, we analyzed retinas of the rd10 mouse, a model for retinitis pigmentosa, with severe degeneration of photoreceptors to determine whether high levels of 8OHdG/8OHG staining intensity in RGCs of control animals is related to the high level of mitochondrial oxidative phosphorylation necessary to support light-evoked RGC activity. 8OHdG/8OHG were almost exclusively associated with mitochondrial DNA/RNA: ~ 65% of 8OHdG/8OHG were associated with RNA isolated from mitochondrial fraction and ~ 35% with DNA. The levels for these oxidized DNA/RNA products were 3.2 and 2.8 fold higher at 1 and 2 weeks after intraocular pressure elevation compared to control retinas, respectively. Immunohistochemical data indicate a predominant localization of 8OHdG/8OHG in retinal ganglion cells (RGCs). This study examines retinas from a rat glaucoma model for oxidized nucleosides 8OHdG and 8OHG, biomarkers for oxidative damage of DNA and RNA, respectively. ![]() Our work reveals surprisingly rich dynamics of post-transcriptional reactions and a potentially widespread mechanism underlying development, tissue regeneration, and cancer cell heterogeneity. The global bifurcation organizing this divergence relies on an oscillator and bistable switch which cannot be decomposed into two structural modules. Diverging oscillation periods synergize with noise to robustly restore cell populations’ bimodal expression on timescales of days. We use mass-action-based models to show that regulated RNA degradation involving as few as two RNA species-applicable to nearly half of human protein-coding genes-can generate sustained oscillations without explicit feedback. Oscillation and noise have been proposed to support mammalian progenitor cells’ capacity to restore heterogenous, multimodal expression from extreme subpopulations, but underlying networks and specific roles of noise remained elusive. Studies of oscillatory expression have focused on networks with intuitive regulatory negative feedback loops, leaving unknown whether other common biochemical reactions can produce oscillations. Periodic gene expression dynamics are key to cell and organism physiology. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells. The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 3'-untranslated region (UTR) and CpG di-nucleotides in the 5'-UTR. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). Median estimated half-life was 7.1 h and only <100 genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. However, the rate of mRNA decay for the majority of genes is not known. Degradation of mRNA is one of the key processes that control the steady-state level of gene expression.
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