What does it mean if a specific treatment strategy reduces the cytosolic expressions of certain proteins but does not alter the expression of the same protein at the mRNA level?
Does it mean that the strategy is not affecting the process of synthesis of the specific protein for instance a cytokine?
Reduction at the protein level while the mRNA level remains stable can point to several things. The main thing you can conclude is that the treatment does not affect the transcriptional activity of your gene of interest as the mRNA level is stable. A reduced protein level can point to a defect in the translational process from mRNA to Protein (ie. ribosomal defect). It can, however, also point to an increased turnover rate of the protein meaning it is degraded faster. Another interpretation is that there could be an issue with the post-translational modifications of the protein, if any are present, causing them to be less stable.
Reduction at the protein level while the mRNA level remains stable can point to several things. The main thing you can conclude is that the treatment does not affect the transcriptional activity of your gene of interest as the mRNA level is stable. A reduced protein level can point to a defect in the translational process from mRNA to Protein (ie. ribosomal defect). It can, however, also point to an increased turnover rate of the protein meaning it is degraded faster. Another interpretation is that there could be an issue with the post-translational modifications of the protein, if any are present, causing them to be less stable.
I agree with my colleagues and want to add one more point/option; with the treatment you may also induce the expression of a miRNA cluster that targets the mRNA of the protein. This could lead to a decreased protein level, too.
As Peter rightly says, a induction of a miRNA cluster could target the mRNA of the protein but wouldn't this be visible at the mRNA level as well? As the mRNA level is unchanged, miRNA wouldn't be a viable option.
Hi Toon, I don't fully agree with your conclusion here. miRNA effects can be timing events. It needs time course evaluation. There has been a nice blog some time ago on this ttopic : https://www.researchgate.net/post/Should_we_see_mRNA_downregulation_caused_by_microRNA_upregulation
So in my opinion regulation by miRNA should be considered, too.
To add another option which often isn't considered:
It is certainly possible that your particular mRNA transcript undergoes controlled downregulation of translation and that this is a deliberate activity rather than being a feature of a defect in translation etc.. There are several proteins - TTP, HuR etc. - that bind to particular motifs in mRNA (e.g. AU-rich elements, AREs) and repress their translation. Furthermore, post-transcriptional control of translatability of the mRNA by, for example, cytosolic polyadenylation by GLD-2 or GLD-4 can control the extent of translation of an mRNA in transcriptionally silent cells or in regionally-restricted mRNAs (e.g. in early stage embryos or at neuronal synapses). While it is true that steady mRNA levels but decreased protein levels are indicative of either increased protein degradation or decreased protein production without mRNA changes, the decreased protein production does not necessarily need to be a feature of some defect or problem with the cell but can be a biologically relevant control method used by the cell.
Hope that helps!
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