However, the mature miRNA levels showed variable tendencies. It is possible that each miRNA has its own half-life and in the event that the miRNA are highly stable, they will not degrade easily, and therefore their levels will remain unchanged. In addition, blocking hnRNPH1 may result in slowing of the miRNA processing but it might not completely arrest it, therefore some miRNAs will still be processed. Over-expression of hnRNPH1 did not show any significant changes in miRNA levels. This might be explained by the fact that hnRNPH1 exists in saturated levels in the cell and therefore over-expression does not affect the miRNA processing. The binding experiment with hnRNPH1 showed that there is a correlation between the binding of hnRNPH1 to a certain pri-miRNA and the contribution of this protein to miRNA processing, as implicated from the siRNA experiment. MiRNAs that showed this tendency are miR-106b, miR-25, miR-224, miR-196b, miR-21, miR-23b and miR-34a. These results support the hypotheses that hnRNPH1 affects miRNA processing through binding to pri-miRNAs. Taken together these results support our hypothesis that hnRNPR and hnRNPH1 exhibit a direct role in the processing of pri-miRNAs. In addition we show for the first time that hnRNPR exhibits an inhibitory activity whereas hnRNPH1 exhibits a facilitating role during miRNA processing. These activities are presumably mediated by their binding to the primiRNAs. In addition our results indicate that there is a great PF-04979064 versatility and variability in the processing of different miRNAs in HeLa cells. This variability could stem from the involvement of certain factors like hnRNPR and hnRNPH1 which might exhibit different affinities to different pri or pre-miRNAs. The advantage of regulation of specific miRNAs through their processing provides the cell means to temporarily regulate the activity of the miRNAs so that it would not reduce the levels of important targets prematurely. The accumulation of pri/pre-miRNAs OSU6162 hydrochloride within the cells enables the cell to respond rapidly when the miRNA is needed.