To determine whether translational repression is involved when miRNAs exert their repressive effects against nonsense mRNAs, we constructed a modified luciferase reporter that has a fragment containing two in-frame miR-125b miREs followed by an additional in-frame stop codon fused to the 3′ end of the luciferase ORF (TAA-2E).
NMD exerts its repressive power primarily by promoting RNA degradation; however, miRNA-mediated repression usually involves both mRNA decay and translational repression.
There are two models to explain the repressive effects that miRNAs exert on target gene expression: i-translational repression and ii-mRNA degradation [16], [17], [42].
If asynapsis persists at the pachytene stage, ATR leads to the induction of repressive post-translational modifications and irreversible gene silencing over many megabases [ 75].
In our analysis, we noticed that post-translational modifications associated with repressive chromatin structure are profoundly impacted as compared to those associated with transcriptionally active, yet these changes move in opposite directions; H3K27 me3 is lost while H3K9 me2 is gained.
Except for changes in H3K27m3 levels in septic organs (Fig. 7), analysis of repressive post-translational modifications H3K9m2, H3K9m3, and H4K20m3 (Additional file 1: Figures S4-S6) revealed no significant ALI-sepsis-induced changes at the angiogenic genes in the lung, kidney, and liver.
In other words, MBDs form bridges between the methylated DNA and histone modifiers that generate repressive histone post-translational modifications.
As such, there are clear examples of specific histone modifier enzymes, particularly those that generate repressive histone post-translational modifications, being physically recruited to the site of DNA replication to re-establish the histone post-translational modifications [ 37, 38].
Di- or trimethylations of the H3-K9 mare are prominent post-translational modifications mostly associated with transcriptionally repressive heterochromatin complex and are the main processes involved in X-chromosome inactivation.
Silencing of HuR did not affect the stability of caspase-2 mRNA but resulted in an increased redistribution of caspase-2 transcripts from RNP particles to translational active polysomes implicating that HuR exerts a direct repressive effect on caspase-2 translation.
