Sebastián Rivera Pérez 3d Semester Medicine student Universidad Pontífice Bolivariana
In this study the scientists report that one of argonautes protein called Ago2 has a different role inasmuch as its help generate microRNAs instead. Ago2 functions as a slicer enzyme that chops up its targets -- messenger RNAs encoded by genes -- by using small RNA molecules as guides to home in on the correct messenger RNAs.
During the study researchers produced mice with catalytically inactive Ago2 and found that their offspring suffered from anemia and that heir lack of catalytically active Ago2 hampers their normal postnatal development. Further experiments showed that the absence of miR-451 in the mutant mice was due not to a defect in its production but the subsequent "maturation
Most of the microRNA are matured in two steps, first performed by the enzyme Drosha and the second step by the enzyme Dicer. But in this study found that miR-451 proceeds via a different maturation pathway, where the Dicer step is skipped and the immature hairpin Into Ago2 is loaded directly
The current study used knockout mice in which the miR-451 gene was removed and could not function. And they found that preventing the activity of miR-451 produced only mild anemia in the mice, but when the scientifics subjected mice to oxidant stress by dosing them with a drug that produces free radicals, the mice had profound anemia.
“ The microRNA frequently don't play a central role during tissue formation or normal conditions, but they have a strong protective effect when an organism is stressed ” Mitchel Weiss Over evolutionary time, red blood cells have evolved ways to protect themselves; one of those ways is the action of microRNA.
The miR-451, acting through intermediate steps on a signaling pathway, affects a key protein, FoxO3. As a transcription factor, FoxO3 regulates hundreds of genes; in this case, FoxO3 stimulates specific genes that protect red blood cells from oxidant stress
Facing the discovery of the effect of Ago2 in the generation of miR-450 is a natural regulator of the production of red blood cells can develop therapies for diseases of erythrocytes and some cancers.
FoxO3 that is regulated for miR-451 regulates anti-oxidant functions in heart cells and also acts as a tumor suppressor, so miR-451 may have an important role in heart protection and in fighting cancers.
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Hannon G, scientists uncover alternative pathway of microRNA generation. Sciencedaily . 2010 July 1
Weiss M. Red blood cells have a tiny a but effective protector: microRNA. Sciencedaily.2010 August 22