Regulation of miRNA gene transcript

Regulation of miRNA gene transcriptionTranscription of miRNA genes is regulated in a similar manner to that of protein-coding genes, and is a major level of control responsible for tissue-specific or development-specific expression of miRNAs. Some examples of transcriptional control are summarized in BOX 3 and are also discussed in recent reviews7,8. Below, we only discuss a few aspects that are specifically related to miRNAs.Control of gene expression by autoregulatory feedback loops is a common regulatory mechanism that is particularly important during cell fate determination and development. miRNAs are uniquely suited to participate in feedback circuits owing to their potential to directly base-pair with and repress mRNAs that encode factors involved in the biogenesis or function of the same miRNAs. Indeed, many examples have been described of miRNAs regulating their own transcription through single-negative or double-negative (or positive) feedback loops with specific transcription factors. For instance, the PITX3 transcription factor and miR-133b form a negative autoregulatory loop that controls dopaminergic neuron differentiation. PITX3 stimulates transcription of miR-133b, which in turn suppresses PITX3 expression9. More sophisticated regulation is provided by doublenegative feedback loops like the one involving miRNAs lys-6 and miR-273, and transcription factors DIe-1 and COG-1 in Caenorhabditis elegans (BOX 3). This loop is instrumental in determining cell fate decisions between two alternative types of chemosensory neurons10. By fine-tuning miRNA expression and adjusting it to physiologically optimal levels, the circuits described above have a strong impact on the precise spatiotemporal expression of miRNA targets.