MicroRNA Regulation in a ‘Positive-Feedback Loop’

Autoregulation of microRNA biogenesis by let-7 and Argonaute

Researchers at University of California, San Diego and Stockholm University have recently provided evidence that microRNA can function in two new capacities:

  1. RISC containing let-7 miRNA can bind and regulate its own primary transcript , inducing  let-7 expression in a positive-feedback dynamic,
  2. RISC can bind to other non-coding RNA species involved with the biogenesis of mature miRNA species, influencing and regulating mature miRNA levels

Using let-7 in C. elegans as an example, Zisoulis et al. was able to additionally identify this regulatory network in HeLa cells, indicating that these networks are present in human development and physiology. The authors hinted at the possibilities within RNA therapeutics by concluding their article saying, “our demonstration of direct miRNA regulation of let-7 biogenesis adds to the growing list of factors that impose post-transcriptional control on a production of this important miRNA. Because misregulation of let-7 leads to disease, the let-7 positive-feedback loop presents a new target for therapeutic interventions designed to restore appropriate miRNA levels.”

Undoubtedly this opens the door for future investigations. It will be interesting to see how complex and involved miRNA biogenesis becomes with this additional layer of regulation.

Figure 1:

Argonaute binds and regulates pri-let-7.


Autoregulation of microRNA biogenesis by let-7 and Argonaute.
Zisoulis, D. G., Kai, Z.S., Chang, R.K., and Amy Pasquinelli.
– 28 June 2012 (Vol. 486, Issue 7401, pp. 541-544)


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