I am sure if the binding site of a microRNA can be implicated on a gene or mRNA there one can conclude about the mechanism of action and in a cancer case, its parthenogenesis.
Is the binding on both 3' and 5' end of mRNA, just 3' UTR or other coding region?
Recall also that they have multiple targets, if this microRNA binds to more than one sites, can can one implicate the specific one responsible for regulation?
Hi fadaka
U r right .mirna do target multiple mrna to regulate translation and in some case transcript stability.it is really challenging to seek exact one target ,e.g. mirna duwnregulated could be regulating protein stability by targeting e3 in ligase and also regulating transcript stability.
Best way is to use mimic or inhibitor and look out for phenotype in terms of assays like flow cytometry or rtpcr or western.
MicroRNA binding is rather complicated with many different cases! Binding in 5' UTR and Open Reading Frame (ORF) has been demonstrated in addition with the most efficient binding region of 3'UTR. To quote the recent review of Bartel, in Cell 2018, "Nonetheless, the 6 nt sites that either match only the seed or are offset by one nucleotide in either the 5' or 3' direction (Figure 5A) can sometimes also mediate detectable repression (Friedman et al., 2009; Jan et al., 2011; Kim et al.,
2016a), as can 7–8 nt sites in open reading frames (ORFs) or 5' UTRs (Lewis et al., 2005; Stark et al., 2007b; Schnall-Levin et al., 2010; Agarwal et al., 2017)."
Multiple binding of the same microRNA to many sites in the 3'UTR region of the target mRNA has also been shown and proved to be additive or even more efficient depending on the distance of the target sites (to each others and/or the ORF).
Related to your second question, I think there are experiments identifying the most efficient target sites for a given mRNA target (doing genetic construction), but I don't have in mind the references.
Another practical things to add,mature mirna only 10 percent associates to ago2 or risk reading 90 %mirna associates strangely to mirbps.so still it is black box what is exact role of a particular mirna in terms of target.as u know risc associated will take part in translational repressing or transcript stability or putting mRNA to p body for degradation or affecting methylation of mRNA or affecting transcription in nucleus like promoter. It is still code which we do not know
miRNA are highly conserved RNA sequence (approx 22 nucleotide long) usually binds to 3' UTR, thereby regulating the expression of mRNA via mRNA cleavage. They play pivotal role in regulation of cell growth, cell mobility, and cell differentiation. However, miRNAs have shown to play crucial role in cancer either by activating oncogenes or inhibiting tumor suppressors. In general, miRNA can promote cancer by targeting the mRNA of tumor suppressor genes (TSGs), this lead to loss of TSGs properties which is attributed to cancer example are; miRNA-373: related to tumor invasion and metastasis, miRNA-221 and 222: related to abnormal cell proliferation, these are referred to as onco-miRNA; however, miRNA can also prevent cancer by binding to the mRNA of oncogenes leading to down-regulation of oncogenes i.e. miRNA-31: prevention against metastasis.
Conclusively, when you say miRNA has multiple targets, yea, but perhaps to mRNA of genes of the-same family or closely related genes. miRNA doesn't bind at random that is why they are used as drugs, remember something that doesn't bind to specific target can not be used as drug.
Kind regards,
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