RRC ID 55695
Author Chatterji P, Williams PA, Whelan KA, Samper FC, Andres SF, Simon LA, Parham LR, Mizuno R, Lundsmith ET, Lee DS, Liang S, Wijeratne HS, Marti S, Chau L, Giroux V, Wilkins BJ, Wu GD, Shah P, Tartaglia GG, Hamilton KE.
Title Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1.
Journal EMBO Rep
Abstract 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 (Imp1Δ IEC ) 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 Imp1Δ IEC mice exhibit enhanced recovery following dextran sodium sulfate (DSS)-mediated colonic injury. Imp1Δ IEC 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 Imp1Δ IEC 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.
Volume 20(6)
Published 2019-6-1
DOI 10.15252/embr.201847074
PII embr.201847074
PMID 31061170
PMC PMC6549032
MeSH Adult Aged Animals Autophagy / genetics Autophagy-Related Protein 7 / genetics Autophagy-Related Protein 7 / metabolism Biomarkers Case-Control Studies Cell Line Colitis, Ulcerative / genetics Colitis, Ulcerative / metabolism Colitis, Ulcerative / pathology Colon Crohn Disease / genetics Crohn Disease / metabolism Crohn Disease / pathology Disease Models, Animal Female Gene Deletion Gene Expression Regulation Genetic Predisposition to Disease Humans Immunohistochemistry Intestinal Mucosa / metabolism* Intestinal Mucosa / pathology Male Mice Middle Aged Paneth Cells / metabolism Paneth Cells / pathology Protein Binding Protein Biosynthesis RNA Processing, Post-Transcriptional RNA, Messenger / genetics RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism Wound Healing / genetics* Young Adult
IF 8.383
Times Cited 2
Mice RBRC02759