1. Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1
- Author
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Kathryn E. Hamilton, Lauren Simon, H. R. Sagara Wijeratne, Shun Liang, Stefanie Marti, David Lee, Fernando Cid Samper, Sarah F. Andres, Priya Chatterji, Louis Parham, Premal Shah, Gian Gaetano Tartaglia, Veronique Giroux, Emma Lundsmith, Gary D. Wu, Lillian Chau, Benjamin J. Wilkins, Kelly A. Whelan, Patrick A. Williams, and Rei Mizuno
- Subjects
colitis ,Mutant ,RNA-binding protein ,RNA-binding proteins ,wound healing ,protein binding ,Biochemistry ,0302 clinical medicine ,middle aged ,colonic repair ,animal ,RNA Processing, Post-Transcriptional ,humans ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,IGF2BP1 ,Chemistry ,adult ,cell line ,gene expression regulation ,Articles ,crohn disease ,IMP1 ,inflammatory bowel disease ,RNA binding protein ,aged ,animals ,autophagy ,autophagy-related protein 7 ,biomarkers ,case-control studies ,colitis, ulcerative ,colon ,disease models, animal ,female ,gene deletion ,genetic predisposition to disease ,immunohistochemistry ,intestinal mucosa ,male ,mice ,paneth cells ,protein biosynthesis ,RNA processing, post-transcriptional ,RNA, messenger ,young adult ,Cell biology ,medicine.anatomical_structure ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Corrigendum ,MAP1LC3B ,ulcerative ,ATG5 ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Genetics ,RNA, Messenger ,Molecular Biology ,030304 developmental biology ,post-transcriptional ,disease models ,Autophagy ,Epithelium ,digestive system diseases ,messenger ,Disease Models, Animal ,RNA processing ,Paneth cell ,RNA ,Colitis, Ulcerative ,030217 neurology & neurosurgery - 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 ( Imp1 Δ IEC ) was associated with better regeneration in mice after irradiation. Here, we report increased IMP1 expression in patients with Crohn9s disease and ulcerative colitis. We demonstrate that Imp1 Δ IEC mice exhibit enhanced recovery following dextran sodium sulfate (DSS)‐mediated colonic injury. Imp1 Δ 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 Imp1 Δ 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.
- Published
- 2019