MicroRNAs Repress Mainly through mRNA Decay

Abstract

Inhibition or degradation? MicroRNAs have been considered primarily as inhibitors of translation, even though degradation of mRNAs also plays a role in their repressive potential. Two research groups have now quantified the extent to which each mechanism contributes to gene regulation by combining mass spectrometry with transcriptome profiling. The surprising conclusion is that translational inhibition plays only a minor role!

DrosophilamiR-277 controls branched-chain amino acid catabolism and affects lifespan

“…The need for experimental validation has been recognized early on and since miRNA-mediated repression also stimulates mRNA degradation, powerful technologies available for transcriptome analysis can be employed. While the relative importance of translational inhibition vs. mRNA degradation remains a matter of debate, parallel analysis via quantitative proteomics and transcriptomics have demonstrated that both approaches will in most cases identify the same targets 36 - 38 , 65 . Thus, inhibition of a given miRNA will increase and overexpression will reduce steady-state levels of its target mRNAs.…”

Regulation of MiR-124, Let-7d, and MiR-181a in the Accumbens Affects the Expression, Extinction, and Reinstatement of Cocaine-Induced Conditioned Place Preference

“…Apart from translational repression, miRNAs can also cause degradation of the target mRNAs. In vitro overexpression of miR-124 decreases the transcripts of 174 genes (Lim et al, 2005) and some studies suggest that translational inhibition plays only a minor role (Baek et al, 2008;Selbach et al, 2008;Esslinger and Förstemann, 2009). This would explain the decrease in the transcript levels of direct and indirect target genes observed by qRT-PCR, which for most genes, correlates with the protein levels found in western blots.…”

“…In addition to translational inhibition, miRNAs can downregulate a large number of target mRNAs (Lim et al, 2005;Baek et al, 2008;Selbach et al, 2008) and may play a major role in mRNA decay (Esslinger and Förstemann, 2009). To check this in the context of cocaine CPP, based on computational and available experimental data on miRNA-target gene interactions (Chandrasekar and Dreyer, 2009), we analyzed mRNA levels of various plasticity genes from the NAc region of different groups after the behavioral experiments ( Figure 6 and Supplementary Tables S1 and S2).…”

“…Interpretation of the observed changes in gene transcripts is complicated, as the data also reflect secondary effects. The effects may also be indirectly caused by the miRNA through the deregulation of a direct target like a transcription factor (CREB, FosB, Myt1, NAC1, and so on) and could result from altered transcriptional output and hyper-repression of the transcription factors (Esslinger and Förstemann, 2009). In general, our data strongly support recent studies where miR-212 with homeostatic interactions with MeCP2 has been reported to be upregulated in the dorsal striatum upon extended (but not restricted) cocaine access and regulates vulnerability to cocaine addiction (Hollander et al, 2010;Im et al, 2010).…”

Towards identifying New Human Ribonucleases that Cleave microRNA Using a High-Throughput Method.

“…MicroRNAs control gene expression through either translational repression or degradation of mRNA (Cai et al 2010;Esslinger et al 2009). They have a huge impact on the global expression of proteins (Baek et al 2008); about half of all mammalian protein coding genes are predicted to be controlled by these versatile regulatory elements (Krol et al 2010).…”