02510nas a2200205   4500008004100000022001400041245017400055210006900229260010600298300001200404490000700416520161600423653002602039653002302065653001002088653003602098100002102134700002302155856012602178       2015                        eng d  a1355-838200aMathematical modeling of combinatorial regulation suggests that apparent positive regulation of targets by miRNA could be an artifact resulting from competition for mRNA0 aMathematical modeling of combinatorial regulation suggests that   a1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USAbCOLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPTcMAR  a307-3190 v213 a<p>MicroRNAs bind to and regulate the abundance and activity of target messenger RNA through sequestration, enhanced degradation, and suppression of translation. Although miRNA have a predominantly negative effect on the target protein concentration, several reports have demonstrated a positive effect of miRNA, i.e., increase in target protein concentration on miRNA overexpression and decrease in target concentration on miRNA repression. miRNA-target pair-specific effects such as protection of mRNA degradation owing to miRNA binding can explain some of these effects. However, considering such pairs in isolation might be an oversimplification of the RNA biology, as it is known that one miRNA interacts with several targets, and conversely target mRNA are subject to regulation by several miRNAs. We formulate a mathematical model of this combinatorial regulation of targets by multiple miRNA. Through mathematical analysis and numerical simulations of this model, we show that miRNA that individually have a negative effect on their targets may exhibit an apparently positive net effect when the concentration of one miRNA is experimentally perturbed by repression/overexpression in such a multi-miRNA multitarget situation. We show that this apparent unexpected effect is due to competition and will not be observed when miRNA interact noncompetitively with the target mRNA. This result suggests that some of the observed unusual positive effects of miRNA may be due to the combinatorial complexity of the system rather than due to any inherently unusual positive effect of the miRNA on its target.</p>10acombinatorial binding10amathematical model10amiRNA10apost-transcriptional regulation1 aNyayanit, Dimpal1 aGadgil, Chetan, J.  uhttps://library.ncl.res.in/content/mathematical-modeling-combinatorial-regulation-suggests-apparent-positive-regulation-0