HuR counteracts miR-330 to promote STAT3 translation during inflammation-induced muscle wasting

Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17261-17270. doi: 10.1073/pnas.1905172116. Epub 2019 Aug 12.


Debilitating cancer-induced muscle wasting, a syndrome known as cachexia, is lethal. Here we report a posttranscriptional pathway involving the RNA-binding protein HuR as a key player in the onset of this syndrome. Under these conditions, HuR switches its function from a promoter of muscle fiber formation to become an inducer of muscle loss. HuR binds to the STAT3 (signal transducer and activator of transcription 3) mRNA, which encodes one of the main effectors of this condition, promoting its expression both in vitro and in vivo. While HuR does not affect the stability and the cellular movement of this transcript, HuR promotes the translation of the STAT3 mRNA by preventing miR-330 (microRNA 330)-mediated translation inhibition. To achieve this effect, HuR directly binds to a U-rich element in the STAT3 mRNA-3'untranslated region (UTR) located within the vicinity of the miR-330 seed element. Even though the binding sites of HuR and miR-330 do not overlap, the recruitment of either one of them to the STAT3-3'UTR negatively impacts the binding and the function of the other factor. Therefore, together, our data establish the competitive interplay between HuR and miR-330 as a mechanism via which muscle fibers modulate, in part, STAT3 expression to determine their fate in response to promoters of muscle wasting.

Keywords: HuR; STAT3; microRNA; muscle wasting; posttranscriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • ELAV-Like Protein 1 / genetics
  • ELAV-Like Protein 1 / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Protein Biosynthesis*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / genetics


  • 3' Untranslated Regions
  • ELAV-Like Protein 1
  • Elavl1 protein, mouse
  • MIRN330 microRNA, mouse
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • STAT3 Transcription Factor
  • Stat3 protein, mouse