A Functional Non-coding RNA Is Produced from xbp-1 mRNA

Neuron. 2020 Sep 9;107(5):854-863.e6. doi: 10.1016/j.neuron.2020.06.015. Epub 2020 Jul 7.


The xbp-1 mRNA encodes the XBP-1 transcription factor, a critical part of the unfolded protein response. Here we report that an RNA fragment produced from xbp-1 mRNA cleavage is a biologically active non-coding RNA (ncRNA) essential for axon regeneration in Caenorhabditis elegans. We show that the xbp-1 ncRNA acts independently of the protein-coding function of the xbp-1 transcript as part of a dual output xbp-1 mRNA stress response axis. Structural analysis indicates that the function of the xbp-1 ncRNA depends on a single RNA stem; this stem forms only in the cleaved xbp-1 ncRNA fragment. Disruption of this stem abolishes the non-coding, but not the coding, function of the endogenous xbp-1 transcript. Thus, cleavage of the xbp-1 mRNA bifurcates it into a coding and a non-coding pathway; modulation of the two pathways may allow neurons to fine-tune their response to injury and other stresses.

Keywords: C. elegans; RNA processing; XBP1; axon regeneration; ncRNA; neuronal injury response; non-coding RNA; xbp-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics*
  • Carrier Proteins / genetics*
  • Nerve Regeneration / genetics*
  • RNA, Messenger / genetics*
  • RNA, Untranslated / genetics*
  • Unfolded Protein Response / genetics


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • RNA, Messenger
  • RNA, Untranslated
  • XBP-1 protein, C elegans