Post-transcriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1.

Chatterji P, Williams PA, Whelan KA, Samper FC, Andres SF, Simon LA, Parham LR, Mizuno R, Lundsmith ET, Lee DSM, Liang S, Wijeratne HRS, Marti S, Chau L, Williams PA, Giroux V, Wilkins BJ, Wu GD, Shah P, Tartaglia GG, Hamilton KE

EMBO reports 20 : e47074



RNA binding proteins, including IMP1/IGF2BP1, are essential regulators of intestinal development and cancer. Imp1 hypomorphic mice exhibit gastrointestinal growth defects, yet the specific role for IMP1 in colon epithelial repair is unclear. Our prior work revealed that intestinal epithelial cell-specific Imp1 deletion (Imp1 Δ\DeltaIEC) was associated with better regeneration in mice after irradiation. Here, we report increased IMP1 expression in patients with Crohn's disease and ulcerative colitis. We demonstrate that (Imp1 Δ\DeltaIEC) mice exhibit enhanced recovery following dextran sodium sulfate (DSS)-mediated colonic injury. (Imp1 Δ\DeltaIEC) mice exhibit Paneth cell granule changes, increased autophagy flux, and upregulation of Atg5. In silico and biochemical analyses revealed direct binding of IMP1 to MAP1LC3B, ATG3, and ATG5 transcripts. Genetic deletion of essential autophagy gene Atg7 in (Imp1 Δ\DeltaIEC) mice revealed increased sensitivity of double-mutant mice to colonic injury compared to control or Atg7 single mutant mice, suggesting a compensatory relationship between Imp1 and the autophagy pathway. The present study defines a novel interplay between IMP1 and autophagy, where IMP1 may be transiently induced during damage to modulate colonic epithelial cell responses to damage.