miRNA controls the noise of protein expression

It is well known that some microRNAs can downregulate particular genes. However, for a more extensive use of these small non-coding RNAs, people are still not too clear. A new study shows that miRNA can act as a damper of genomic noise to control the changes of protein expression. The results are published in the journal Science on April 3. There are also other studies about recombinant proteins published in the same journal.

The universality and conservatism of miRNA and its tendency of slightly inhibiting the vast majority of their targets make some people speculate that the function of miRNA is precisely controlling of gene expression among cell populations. In this study, researchers from the Massachusetts Institute of Technology (MIT) and the Humboldt University used mathematical modeling and synthesis of genetics to prove miRNA does provides this type of noise control.

To test the function of the endogenous miRNA, researchers used dual fluorescent protein reporter system to quantify the protein levels and volatility of mouse embryonic stem cells, in which two different reporter genes (ZsGreen and mCherry) are transcribed by a common bidirectional promoter. And recombinant horse proteins and recombinant dog proteins are used. On mCherry reporter gene 3'UTR contains some variation and multiple miRNA binding sites, and researchers used flow cytometry to quantify single-cell fluorescence.

They studied the effects of miR-20a on designing target site in reporter gene. Compared with the control, in cells with low expression of the reporter gene, the noise reduced; while in cells of high expression, the noise increased. It is noteworthy that when the reporter gene of miR-20a target site is ideal or there are multiple sites in the 3'UTR, the change of this noise is particularly evident.

To explore these mechanisms which seem to have opposing effects to each other, the researchers created a mathematical model to decompose the total noise into intrinsic noise (i.e. changes of protein expression produced the random process of protein production as well as external noise (i.e. the changes produced by fluctuations of external factors).

This model predicted the effects of miRNA regulation on different types of noise, compared with the genes which were not regulated, intrinsic noise of genes which were regulated by miRNA reduced. Meanwhile, miRNA regulation was expected to increase the external noise. Taken together, this model predicted that the net effect of inherent noise reduction and external noise increase will result in the reduction of low-expressed total noise, while the total noise of high expression increased.

To test this prediction experimentally, the researchers changed the reporting system by making the two reporter genes contain the same 3'UTR, while their expression difference only came from the processing of each gene, namely the inherent noise. They found that the regulation of miR-20a reduced the intrinsic noise, which was consistent with the prediction of mathematical model. Further experiments showed that genes regulated by multiple miRNAs experienced a more pronounced noise reduction. Flarebio provides different recombinant proteins such as recombinant CDH10 for your research.

The researchers believed that these results indicated miRNA make sure of the accuracy of protein expression and explained the phenomenon that is commonly observed that endogenous gene is targeted by a plurality of miRNA combinations as well as preferential of genes with low expression.