Figure 3

Intricate network of regulation of let-7 expression and activity by different proteins. Multiple mechanisms give rise to an intricate feed-back loop which controls the expression of let-7 and Lin-28. Lin28, which is highly expressed in undifferentiated, embryonic stem cells, selectively blocks the processing of let-7 miRNAs through multiple mechanisms including Drosha blockade, Dicer blockade, and 3'-uridylation of pre-let-7. The highly regulated expression of let-7 is critical for the control of cellular differentiation and proliferation.