However, it has been demonstrated that although some targets are repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA decreases, and, for the more highly repressed targets, mRNA degradation usually comprised the major component of repression.
For the more highly repressed targets, mRNA destabilization usually constituted the major component of repression [ 14], thus making the investigation of the mRNA:miRNA association by monitoring miRNA and mRNA expression on a genome-wide basis a novel analytical approach to understand the miRNA-mediated regulation [ 15, 16].
Two large scale proteomic studies published very recently have shown that, although some microRNA target proteins are repressed without detectable changes in mRNA levels, more than a third of translational repressed targets also display detectable mRNA destabilization and, for the more highly repressed targets, mRNA destabilization usually makes up the major component of repression [ 19, 20].
Nonetheless, there is increasing evidence that the translational effect of microRNAs is accompanied by changes in mRNA level, and that mRNA destabilization is the dominant component of repression.
The component of repression on the translational level accounts for the stronger reduction of protein than mRNA levels and is apparent at 24 hours, becoming more evident at later time points (see Fig. 2A).
We applied the Reporter Feature algorithm to analyze the transcriptional response of different S. cerevisiae mutants with deletions in key components of glucose repression (namely Δ grr1, Δ hxk2, Δ mig1, Δ mig1mig2 and Δ rgt1 [ 9, 11]).
An important component of HSF1 repression occurs through the phosphorylation of serine 303 and serine 307 [18], [18].
A key component of PcG repression is the histone methyltransferase EZH2 (enhancer of zeste homolog 2), the enzymatic core component of the Polycomb repressive complex 2 (PRC2).
The absence of robust Piwil2 expression in the placenta (Fig. 2A and B) could reflect the activity of the residual ∼40% methylation at this promoter, or the DNA methylation-independent component of Piwil2 repression that is evident upon differentiation of Dnmt3a −/− Dnmt3b −/− ES cells (17).
The chromobox proteins (CBX2, 4, 6, 7, and 8) are critical components of PcG-mediated repression.
