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

Priya Chatterji; Patrick A. Williams; Kelly A. Whelan; Fernando C. Samper; Sarah F. Andres; Lauren A. Simon; Louis R. Parham; Rei Mizuno; Emma T. Lundsmith; David S.M. Lee; Shun Liang; HR Sagara Wijeratne; Stefanie Marti; Lillian Chau; Veronique Giroux; Benjamin J. Wilkins; Gary D. Wu; Premal Shah; Gian G. Tartaglia; Kathryn E. Hamilton

doi:10.15252/embr.201847074

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

Priya Chatterji, Patrick A. Williams, Kelly A. Whelan, Fernando C. Samper, Sarah F. Andres, Lauren A. Simon, Louis R. Parham, Rei Mizuno, Emma T. Lundsmith, David S.M. Lee, Shun Liang, HR Sagara Wijeratne, Stefanie Marti, Lillian Chau, Veronique Giroux, Benjamin J. Wilkins, Gary D. Wu, Premal Shah, Gian G. Tartaglia, Kathryn E. Hamilton

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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 Crohn's 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.

Original language	English (US)
Article number	e47074
Journal	EMBO Reports
Volume	20
Issue number	6
DOIs	https://doi.org/10.15252/embr.201847074
State	Published - Jun 2019
Externally published	Yes

Keywords

IGF2BP1
IMP1
RNA binding protein
colonic repair
inflammatory bowel disease

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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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, HR. S., Marti, S., Chau, L., Giroux, V., Wilkins, B. J., Wu, G. D., Shah, P., Tartaglia, G. G., & Hamilton, K. E. (2019). Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. EMBO Reports, 20(6), Article e47074. https://doi.org/10.15252/embr.201847074

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, Giroux, V, Wilkins, BJ, Wu, GD, Shah, P, Tartaglia, GG & Hamilton, KE 2019, 'Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1', EMBO Reports, vol. 20, no. 6, e47074. https://doi.org/10.15252/embr.201847074

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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.",

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author = "Priya Chatterji and Williams, {Patrick A.} and Whelan, {Kelly A.} and Samper, {Fernando C.} and Andres, {Sarah F.} and Simon, {Lauren A.} and Parham, {Louis R.} and Rei Mizuno and Lundsmith, {Emma T.} and Lee, {David S.M.} and Shun Liang and Wijeratne, {HR Sagara} and Stefanie Marti and Lillian Chau and Veronique Giroux and Wilkins, {Benjamin J.} and Wu, {Gary D.} and Premal Shah and Tartaglia, {Gian G.} and Hamilton, {Kathryn E.}",

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year = "2019",

month = jun,

doi = "10.15252/embr.201847074",

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AU - Samper, Fernando C.

AU - Andres, Sarah F.

AU - Simon, Lauren A.

AU - Parham, Louis R.

AU - Mizuno, Rei

AU - Lundsmith, Emma T.

AU - Lee, David S.M.

AU - Liang, Shun

AU - Wijeratne, HR Sagara

AU - Marti, Stefanie

AU - Chau, Lillian

AU - Giroux, Veronique

AU - Wilkins, Benjamin J.

AU - Wu, Gary D.

AU - Shah, Premal

AU - Tartaglia, Gian G.

AU - Hamilton, Kathryn E.

PY - 2019/6

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N2 - 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.

AB - 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.

KW - IGF2BP1

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KW - colonic repair

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

Abstract

Keywords

ASJC Scopus subject areas

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