Microprocessor of microRNAs: regulation and potential for therapeutic intervention

Abstract

MicroRNAs (miRNAs) are a class of small, noncoding RNAs critically involved in a wide spectrum of normal and pathological processes of cells or tissues by fine-tuning the signals important for stem cell development, cell differentiation, cell cycle regulation, apoptosis, and transformation. Considerable progress has been made in the past few years in understanding the transcription, biogenesis and functional regulation of miRNAs. Numerous studies have implicated altered expression of miRNAs in human cancers, suggesting that aberrant expression of miRNAs is one of the hallmarks for carcinogenesis. In this review, we briefly discuss most recent discoveries on the regulation of miRNAs at the level of microprocessor-mediated biogenesis of miRNAs.

Figure 1

MicroRNA (miRNA) production and processing. The pri-miRNA transcript is transcribed by RNA polymerase II. The stem loop structure is cleaved off by the microprocessor to generate pre-miRNA. The pre-miRNA is exported to the cytoplasm by exportin5 in a ran-GTP dependent manner. Once in the cytoplasm, the pre-miRNA is processed by Dicer creating a single stranded mature miRNA. This mature miRNA is bound by the RISC complex, guiding it to the 3'UTR of target mRNAs, leading to repression of protein expression.

Figure 2

Modulation of microprocessor function by SMAD, p53 and Ars2 in response to TGF-β, p53 and stress signaling, respectively.