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 journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article numbere47074
JournalEMBO Reports
Volume20
Issue number6
DOIs
StatePublished - Jun 2019

Fingerprint

RNA-Binding Proteins
Repair
Enhanced recovery
Autophagy
Dextran Sulfate
Genes
Irradiation
Fluxes
Defects
Epithelial Cells
Paneth Cells
Intestinal Neoplasms
Essential Genes
Wounds and Injuries
Ulcerative Colitis
Crohn Disease
Computer Simulation
Regeneration
Colon
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Keywords

  • IGF2BP1
  • IMP1
  • RNA binding protein
  • colonic repair
  • inflammatory bowel disease

Cite this

Chatterji, P., Williams, P. A., Whelan, K. A., Samper, F. C., Andres, S. F., Simon, L. A., ... Hamilton, K. E. (2019). Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. EMBO Reports, 20(6), [e47074]. https://doi.org/10.15252/embr.201847074
Chatterji, Priya ; Williams, Patrick A. ; Whelan, Kelly A. ; Samper, Fernando C. ; Andres, Sarah F. ; Simon, Lauren A. ; Parham, Louis R. ; Mizuno, Rei ; Lundsmith, Emma T. ; Lee, David S.M. ; Liang, Shun ; Wijeratne, HR Sagara ; Marti, Stefanie ; Chau, Lillian ; Giroux, Veronique ; Wilkins, Benjamin J. ; Wu, Gary D. ; Shah, Premal ; Tartaglia, Gian G. ; Hamilton, Kathryn E. / Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. In: EMBO Reports. 2019 ; Vol. 20, No. 6.
@article{e00437c2a1f743578c452dca5a643fd4,
title = "Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1",
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.",
keywords = "IGF2BP1, IMP1, RNA binding protein, colonic repair, inflammatory bowel disease",
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.}",
year = "2019",
month = "6",
doi = "10.15252/embr.201847074",
language = "English (US)",
volume = "20",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "6",

}

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

Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. / Chatterji, Priya; Williams, Patrick A.; Whelan, Kelly A.; Samper, Fernando C.; Andres, Sarah F.; Simon, Lauren A.; Parham, Louis R.; Mizuno, Rei; Lundsmith, Emma T.; Lee, David S.M.; Liang, Shun; Wijeratne, HR Sagara; Marti, Stefanie; Chau, Lillian; Giroux, Veronique; Wilkins, Benjamin J.; Wu, Gary D.; Shah, Premal; Tartaglia, Gian G.; Hamilton, Kathryn E.

In: EMBO Reports, Vol. 20, No. 6, e47074, 06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1

AU - Chatterji, Priya

AU - Williams, Patrick A.

AU - Whelan, Kelly A.

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

Y1 - 2019/6

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

KW - IMP1

KW - RNA binding protein

KW - colonic repair

KW - inflammatory bowel disease

UR - http://www.scopus.com/inward/record.url?scp=85065341518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065341518&partnerID=8YFLogxK

U2 - 10.15252/embr.201847074

DO - 10.15252/embr.201847074

M3 - Article

C2 - 31061170

AN - SCOPUS:85065341518

VL - 20

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 6

M1 - e47074

ER -

Chatterji P, Williams PA, Whelan KA, Samper FC, Andres SF, Simon LA et al. Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. EMBO Reports. 2019 Jun;20(6). e47074. https://doi.org/10.15252/embr.201847074