Recovery from heat shock requires the microRNA pathway in Caenorhabditis elegans

PLoS Genet. 2021 Aug 5;17(8):e1009734. doi: 10.1371/journal.pgen.1009734. eCollection 2021 Aug.

Abstract

The heat shock response (HSR) is a highly conserved cellular process that promotes survival during stress. A hallmark of the HSR is the rapid induction of heat shock proteins (HSPs), such as HSP-70, by transcriptional activation. Once the stress is alleviated, HSPs return to near basal levels through incompletely understood mechanisms. Here, we show that the microRNA pathway acts during heat shock recovery in Caenorhabditis elegans. Depletion of the miRNA Argonaute, Argonaute Like Gene 1 (ALG-1), after an episode of heat shock resulted in decreased survival and perdurance of high hsp-70 levels. We present evidence that regulation of hsp-70 is dependent on miR-85 and sequences in the hsp-70 3'UTR that contain target sites for this miRNA. Regulation of hsp-70 by the miRNA pathway was found to be particularly important during recovery from HS, as animals that lacked miR-85 or its target sites in the hsp-70 3'UTR overexpressed HSP-70 and exhibited reduced viability. In summary, our findings show that down-regulation of hsp-70 by miR-85 after HS promotes survival, highlighting a previously unappreciated role for the miRNA pathway during recovery from stress.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / genetics
  • Heat-Shock Response / genetics*
  • Heat-Shock Response / physiology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcriptional Activation

Substances

  • ALG-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • MicroRNAs
  • RNA-Binding Proteins