Quantifying negative feedback regulation by micro-RNAs

Phys Biol. 2011 Oct;8(5):055002. doi: 10.1088/1478-3975/8/5/055002. Epub 2011 Aug 10.

Abstract

Micro-RNAs (miRNAs) play a crucial role in post-transcriptional gene regulation by pairing with target mRNAs to repress protein production. It has been shown that over one-third of human genes are targeted by miRNA. Although hundreds of miRNAs have been identified in mammalian genomes, the function of miRNA-based repression in the context of gene regulation networks still remains unclear. In this study, we explore the functional roles of feedback regulation by miRNAs. In a model where repression of translation occurs by sequestration of mRNA by miRNA, we find that miRNA and mRNA levels are anti-correlated, resulting in larger fluctuation in protein levels than theoretically expected assuming no correlation between miRNA and mRNA levels. If miRNA repression is due to a catalytic suppression of translation rates, we analytically show that the protein fluctuations can be strongly repressed with miRNA regulation. We also discuss how either of these modes may be relevant for cell function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Down-Regulation
  • Feedback, Physiological / physiology*
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Genome
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger