Our data demonstrate that a combination of genomic destabilization and genetic polymorphism are influencing the evolution of MPXV strains actively circulating in the Sankuru District of the DRC.
These findings suggest that genetic and epigenetic destabilization of genes at chromosome 3 (especially 3p) are common mechanisms of epithelial tumors development.
In the C. elegans TRNs, MT destabilization induced by genetic or pharmacological manipulations results in not only decreased levels β-tubulin mec-7 mRNA but also a general decrease in protein production, including GFP driven by the mec-7 promoter (Savage et al., 1994; Bounoutas et al., 2011).
Although we cannot formally exclude alternative (e.g., adaptive) recruitment mechanisms for the MS-RPs/OXPHOS proteins, our concept involving deleterious mutations in the mitochondrial genome is supported by 1) well-established recruitment mechanisms; 2) population genetic data, and 3) signs of destabilization in mitochondrial genes.
This destabilization of RNA regulation is uncovered by genetic interaction assays that identify splicing factor knockdowns as genetic enhancers of partial loss-of-function mutations in RNA-binding proteins.
T-cell-specific genetic deficiency in the TGF-β receptor leads to plaque destabilization, whereas regulatory T cells have the ability to reduce atherosclerotic burden in hyperlipidaemic mice [ 43].
Gallbladder hypomotility, destabilization of bile by kinetic protein factors, abnormal mucins and genetic factors also play roles in cholesterol gallstone disease [ 24].
Implications and future directions This model will allow, for the first time, the use of unbiased forward and reverse genetic approaches in a live-animal setting to identify regulators of ΔF508-dependent protein destabilization.
Genetic ablation of only one component results in mislocalization (notably retention in the ER), incomplete maturation and destabilization of the remaining components.
