Regulation of pri-miRNA processing through Smads.

microRNAs (miRNAs) are small (-22 nucleotides (nt)), noncoding RNAs that play a critical role in diverse biological functions by modulating mRNA stability and translational control. Numerous miRNA profiling studies have indicated that the levels of miRNAs are tightly controlled during developmental stages and various pathophysiological and physiological conditions. Following transcription, the long primary miRNA transcript undergoes a series of coordinated maturation steps to generate the mature miRNA. Signaling pathways that control miRNA biogenesis and the mechanisms ofregulation, however, are not well understood. In this chapter, we will discuss the finding that signal transducers of the Transforming Growth Factor beta (TGFbeta) signaling pathway, the Smads, play a critical regulatory role in the nuclear processing of miRNAs by the RNase III-type protein Drosha.