The RHEB-mTOR axis regulates expression of Tf2 transposons in fission yeast

J Cell Sci. 2018 Nov 21;131(22):jcs221457. doi: 10.1242/jcs.221457.


The human TSC2 gene, mutations in which predispose individuals to the disease tuberous sclerosis complex (TSC), encodes a GTPase-activating protein for the GTPase RHEB. Loss of TSC2 results in constitutive activation of RHEB and its target mammalian target of rapamycin (mTOR). We have previously reported that fission yeast (Schizosaccharomyces pombe) Tf2 retrotransposons (hereafter Tf2s) are abnormally induced upon nitrogen starvation in cells lacking the tsc2+ gene (Δtsc2), a homolog of the human TSC2 gene, and in cells with a dominant-active mutation in the fission yeast RHEB GTPase (rhb1-DA4). We report here that induction of Tf2s in these mutants is suppressed upon overexpression of the cgs2+ gene, which encodes a cAMP-specific phosphodiesterase, or upon deletion of components in the glucose/cAMP signaling pathway, namely Cyr1, Pka1, Tor1 and the stress-activated transcription factor Atf1. The results suggest that the glucose/cAMP signaling pathway is downregulated when cells are starved for nitrogen. We also show that Tf2 proteins are degraded via autophagy, which is under control of Tor2, a homolog of human mTOR. It appears that failure in the two processes, downregulation of the glucose/cAMP signaling pathway and induction of autophagy, allows abnormal induction of Tf2s upon nitrogen starvation in Δtsc2 and rhb1-DA4 cells.

Keywords: Autophagy; Glucose/cAMP signaling; Nitrogen starvation; RHEB–mTOR; Transposon; Tuberous sclerosis complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Nitrogen / deficiency
  • Nitrogen / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / biosynthesis*
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*


  • Schizosaccharomyces pombe Proteins
  • Tf2-6 protein, S pombe
  • Tsc2 protein, S pombe
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Monomeric GTP-Binding Proteins
  • Rheb protein, S pombe
  • Nitrogen