Modulation of microRNA activity by semi-microRNAs

The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing theformation of 19–24-nucleotide (nt) long microRNAs. Subsequently incorporated into Arg-onaute 2 (Ago2) effector complexes, microRNAs are known to regulate messenger RNA(mRNA) translation. Whether shorter RNA species derived from microRNAs exist and playa role in mRNA regulation remains unknown. Here, we report the serendipitous discoveryof a 12-nt long RNA species corresponding to the 5′region of the microRNA let-7, and ten-tatively termed semi-microRNA, or smiRNA. Using a smiRNA derived from the precursorof miR-223 as a model, we show that 12-nt long smiRNA species are devoid of any directmRNA regulatory activity, as assessed in a reporter gene activity assay in transfected cul-tured human cells. However,smiR-223 was found to modulate the ability of the microRNAfrom which it derives to mediate translational repression or cleavage of reporter mRNAs.Our findings suggest that the 12-nt RNA species, generated along the microRNA pathway,may participate to the control of gene expression by regulating the activity of the relatedfull-length mature microRNAin vivo