how does the binding of miRNA at 3'UTR regulates the gene - (Jun/29/2011 )
Can anyone help me to understand more about how miRNA regulates a gene? If the 3'UTR of a gene (say A) has a binding site of a miRNA, does that mean that miRNA only regulates that gene (ie A)? Or can it affect any other unrelated gene (eg geneB)? And how do they regulate the gene (eg. suppressor or oncogenes) when it is located at 3'UTR? It seems to be more logical if the location of the miRNA binding site is at 5'UTR, where it might stop or induce the transcription of the gene.
I'm lost here!
"It seems to be more logical if the location of the miRNA binding site is at 5'UTR, where it might stop or induce the transcription of the gene."
MicroRNAs regulate gene expression at post-transcriptional level.
Each microRNA has lots of targets (e.g. around thousand known human microRNAs target 30% of genome). However most of interactions are predicted in silico and not validated experimentally. Upon binding microRNA can either block translation or cause mRNA degradation. The precise mechanisms are mostly unknown.
I've read some papers proposing interactions between the RISC and the initiation factors. The mRNA circularizes before translation, with the 3'-UTR and the 5'-UTR brought close together. This allows interaction between the RISC and the initiation factors, inhibiting the start of translation. Sorry I don't have the citations handy -- they were a few years old. Does anyone know of new work on this?
After went through a few papers, i think i've found the best explanation by McDaneld 2009 J.Anim. Sci, "repression of translation via miRNA is a result of deadenylation of the poly A tail and subsequent decapping of the mRNA sequence. As the result mRNA sequence becomes unstable and susceptible to degradation, resulting in decreased mRNA abundance and subsequent decrease translation"