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MEX3C interacts with adaptor-related protein complex 2 and involves in miR-451a exosomal sorting

Pin Lu1,2, Huanhuan Li2, Ning Li2

  • 1Anhui Normal University, Wuhu, China.

Plos One
|October 6, 2017
PubMed

Insights

The study reveals that RNA-binding protein MEX3C (RNA-binding ubiquitin E3 ligase) interacts with AP-2 to facilitate exosomal sorting of microRNA miR-451a, a process dependent on ceramide but not ESCRT.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Exosome Biology

Background:

  • Exosomes are key mediators of intercellular communication, selectively packaging RNA species like microRNAs.
  • The precise mechanisms governing the selective sorting of RNA into exosomes remain largely unknown.
  • RNA-binding proteins are implicated in RNA localization, but their direct role in exosome sorting is under investigation.

Purpose of the Study:

  • To elucidate the mechanism by which specific microRNAs are sorted into exosomes.
  • To identify the protein machinery involved in the selective exosomal sorting of microRNA miR-451a.
  • To investigate the role of RNA-binding ubiquitin E3 ligase (MEX3C) in microRNA exosomal export.

Main Methods:

  • Investigated interactions between RNA-binding ubiquitin E3 ligase (MEX3C) variants and adaptor-related protein complex 2 (AP-2).
  • Utilized siRNA-mediated inhibition to assess the impact of MEX3C and AP-2 on microRNA expression.
  • Examined the role of ceramide and ESCRT pathways in microRNA exosomal sorting.

Main Results:

  • All three MEX3C variants interact with AP-2, a clathrin-mediated endocytosis adaptor.
  • MEX3C association with the endolysosomal compartment occurs via an endocytosis-like process.
  • Inhibition of MEX3C or AP-2 significantly reduced exosomal miR-451a levels, but not cellular levels.
  • Exosomal sorting of miR-451a was found to be ceramide-dependent and ESCRT-independent.

Conclusions:

  • RNA-binding proteins associate with membrane trafficking machinery to regulate exosome cargo.
  • MEX3C and AP-2 play a crucial role in the selective recruitment of microRNA miR-451a to endosomes for exosomal sorting.
  • This study suggests a novel mechanism for specific RNA recruitment into exosomes, highlighting the importance of ceramide.

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