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Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer

Pascal D Vos1,2,3, Peter J Leedman1,2,4, Aleksandra Filipovska1,2,3

  • 1Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, 6009, Australia.

Cellular and Molecular Life Sciences : CMLS
|June 6, 2019
PubMed

Insights

RNA-binding proteins (RBPs) and microRNAs (miRNAs) are key gene regulators. Understanding their complex interactions, especially in cancer, is crucial for developing new RNA-level gene expression therapies.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Synthetic Biology

Background:

  • RNA-binding proteins (RBPs) and microRNAs (miRNAs) are critical regulators of mRNA stability and translation in eukaryotic cells.
  • The intricate interplay between RBPs and miRNAs, including their opposing regulatory roles on shared targets and cross-regulation of expression levels, is an emerging area of research.
  • Dysregulation of these regulatory circuits is increasingly implicated in cancer development and progression, yet the principles governing their synergistic and antagonistic interactions remain poorly understood.

Purpose of the Study:

  • To elucidate the complex interplay between RNA-binding proteins (RBPs) and microRNAs (miRNAs) in cellular gene regulation.
  • To investigate the mechanisms underlying synergism and antagonism between RBPs and miRNAs, particularly in the context of cancer.
  • To explore the potential of synthetic biology approaches, including artificial RBPs, for understanding and manipulating gene expression at the RNA level for therapeutic applications.

Main Methods:

  • Review and synthesis of existing literature on RNA-binding proteins (RBPs) and microRNAs (miRNAs).
  • Exploration of concepts from synthetic biology for developing artificial systems to study RNA regulation.
  • Discussion of the implications of artificial RNA-binding proteins for understanding RBP-miRNA interactions.

Main Results:

  • RBPs and miRNAs regulate distinct and overlapping mRNA targets, often with opposing effects.
  • The levels of RBPs and miRNAs can influence each other, impacting target gene translation.
  • Artificial RNA-binding proteins offer a novel tool for dissecting functional interactions between RBPs and miRNAs.

Conclusions:

  • The complex interactions between RBPs and miRNAs are fundamental to gene regulation and implicated in cancer.
  • Synthetic biology, particularly with artificial RBPs, holds promise for advancing our understanding and therapeutic manipulation of RNA regulatory networks.
  • Further research into the rules governing RBP-miRNA synergism and antagonism is essential for harnessing their therapeutic potential.
Keywords:
Designer RNA-binding proteinsPUF domainPentatricopeptide repeatRNA interferenceRNA–protein interactionsSynthetic biologymiRNA

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