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Why do miRNAs always bind to 3'UTR? - (Oct/24/2008 )

Does anyone have any ideas about this, or any journals that have mentioned this before? Since translation starts from 5' to 3'end, miRNA binding to 3'utr of its target gene mRNA will waste the resources to do transcription. I am wondering why not just simply binding to 5'UTR and stop the transcription instead??

-Samantha-

miRNA activity is not limited to the 3'-UTR.

MicroRNAs regulate several mouse genes by interacting with miRNA response elements located in the coding region those genes.

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MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation

Yvonne Tay, Jinqiu Zhang, Andrew M. Thomson, Bing Lim & Isidore Rigoutsos

Nature. 2008 Sep 17. [Epub ahead of print] | doi:10.1038/nature07299

MicroRNAs (miRNAs) are short RNAs that direct messenger RNA degradation or disrupt mRNA translation in a sequence-dependent manner1, 2, 3, 4, 5, 6, 7. For more than a decade, attempts to study the interaction of miRNAs with their targets were confined to the 3’ untranslated regions of mRNAs1, fuelling an underlying assumption that these regions are the principal recipients of miRNA activity. Here we focus on the mouse Nanog, Oct4 (also known as Pou5f1) and Sox2 genes8, 9, 10, 11 and demonstrate the existence of many naturally occurring miRNA targets in their amino acid coding sequence (CDS). Some of the mouse targets analysed do not contain the miRNA seed, whereas others span exon–exon junctions or are not conserved in the human and rhesus genomes. miR-134, miR-296 and miR-470, upregulated on retinoic-acid-induced differentiation of mouse embryonic stem cells, target the CDS of each transcription factor in various combinations, leading to transcriptional and morphological changes characteristic of differentiating mouse embryonic stem cells, and resulting in a new phenotype. Silent mutations at the predicted targets abolish miRNA activity, prevent the downregulation of the corresponding genes and delay the induced phenotype. Our findings demonstrate the abundance of CDS-located miRNA targets, some of which can be species-specific, and support an augmented model whereby animal miRNAs exercise their control on mRNAs through targets that can reside beyond the 3’ untranslated region.

-Jon Moulton-

They can also bind the promoter region too (see PMID: 18227514 ). But I think you might find this review (PMID: 17699746) useful as it has a nice model of how the 3' UTR interacts with the 5' UTR and could inhibit initiation of translation (see figure 2 in particular ). If this model is true, then there isn't any wastage of resources.

-miRNA man-

I think 3UTR is involved in the loading of ribosomes.

QUOTE (Samantha @ Oct 24 2008, 01:45 AM)
Does anyone have any ideas about this, or any journals that have mentioned this before? Since translation starts from 5' to 3'end, miRNA binding to 3'utr of its target gene mRNA will waste the resources to do transcription. I am wondering why not just simply binding to 5'UTR and stop the transcription instead??

-yuut-