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 (Imp1ΔIEC) 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 Imp1ΔIEC mice exhibit enhanced recovery following dextran sodium sulfate (DSS)-mediated colonic injury. Imp1ΔIEC 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 Imp1ΔIEC 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.

Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1 / Chatterji, P.; Williams, P. A.; Whelan, K. A.; Samper, F. C.; Andres, S. F.; Simon, L. A.; Parham, L. R.; Mizuno, R.; Lundsmith, E. T.; Lee, D. S. M.; Liang, S.; Wijeratne, H. R. S.; Marti, S.; Chau, L.; Giroux, V.; Wilkins, B. J.; Wu, G. D.; Shah, P.; Tartaglia, G. G.; Hamilton, K. E.. - In: EMBO REPORTS. - ISSN 1469-221X. - 20:6(2019). [10.15252/embr.201847074]

Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1

Tartaglia G. G.;
2019

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 (Imp1ΔIEC) 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 Imp1ΔIEC mice exhibit enhanced recovery following dextran sodium sulfate (DSS)-mediated colonic injury. Imp1ΔIEC 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 Imp1ΔIEC 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.
2019
colonic repair; IGF2BP1; IMP1; inflammatory bowel disease; RNA binding protein; adult; aged; animals; autophagy; autophagy-related protein 7; biomarkers; case-control studies; cell line; colitis, ulcerative; colon; crohn disease; disease models, animal; female; gene deletion; gene expression regulation; genetic predisposition to disease; humans; immunohistochemistry; intestinal mucosa; male; mice; middle aged; paneth cells; protein binding; protein biosynthesis; RNA processing, post-transcriptional; RNA, messenger; RNA-binding proteins; wound healing; young adult
01 Pubblicazione su rivista::01a Articolo in rivista
Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1 / Chatterji, P.; Williams, P. A.; Whelan, K. A.; Samper, F. C.; Andres, S. F.; Simon, L. A.; Parham, L. R.; Mizuno, R.; Lundsmith, E. T.; Lee, D. S. M.; Liang, S.; Wijeratne, H. R. S.; Marti, S.; Chau, L.; Giroux, V.; Wilkins, B. J.; Wu, G. D.; Shah, P.; Tartaglia, G. G.; Hamilton, K. E.. - In: EMBO REPORTS. - ISSN 1469-221X. - 20:6(2019). [10.15252/embr.201847074]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1451185
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