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Polyamines and mRNA stability in regulation of intestinal mucosal growth

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Summary.

The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through strict regulation of epithelial cell proliferation, growth arrest, and apoptosis. Polyamines are necessary for normal intestinal mucosal growth and decreasing cellular polyamines inhibits cell proliferation and disrupts epithelial integrity. An increasing body of evidence indicates that polyamines regulate intestinal epithelial cell renewal by virtue of their ability to modulate expression of various genes and that growth inhibition following polyamine depletion results primarily from the activation of growth-inhibiting genes rather than a simple decrease in expression of growth-promoting genes. In this review article, we will focus on changes in expression of growth-inhibiting genes following polyamine depletion and further analyze in some detail the mechanisms through which mRNA stability is regulated by RNA-binding proteins.

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Abbreviations

AMPK:

AMP-activated protein kinase

AP-1:

activator protein-1

co-Smad:

common-Smad

CR:

coding region

CRE:

cAMP responsive element

C-siRNA:

control siRNA

DENSPM:

N1, N11-diethylnorspermdine

DFMO:

D,L-α-difluoromethylornithine

IEC:

intestinal epithelial cell

I-Smads:

inhibitory Smads

NPM:

necleophosmin

ODC:

ornithine decarboxylase

Q-PCR:

real-time quantitative PCR

R-Smads:

receptor-regulated Smads

siHuR:

siRNA targeting HuR mRNA

siRNA:

small interfering RNA

TGF-β:

transforming growth factor-β

TGFβRII:

TGF-β type II receptor

TRE:

TPA responsive element

3′-UTRs:

3′-untranslated regions

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  1. Cell Biology Group, Departments of Surgery and Pathology, University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA

    J.-Y. Wang

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Wang, JY. Polyamines and mRNA stability in regulation of intestinal mucosal growth. Amino Acids 33, 241–252 (2007). https://doi.org/10.1007/s00726-007-0518-z

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