Post-transcriptional regulation of meprin α by the RNA-binding proteins Hu antigen R (HuR) and tristetraprolin (TTP).

Abstract

Meprins are multimeric proteases that are implicated in inflammatory bowel disease by both genetic association studies and functional studies in knock-out mice. Patients with inflammatory bowel disease show decreased colonic expression of meprin α, although regulation of expression, particularly under inflammatory stimuli, has not been studied. The studies herein demonstrate that the human meprin α transcript is bound and stabilized by Hu antigen R at baseline, and that treatment with the inflammatory stimulus phorbol 12-myristate 13-acetate downregulates meprin α expression by inducing tristetraprolin. The enhanced binding of tristetraprolin to the MEP1A 3'-UTR results in destabilization of the transcript and occurs at a discrete site from Hu antigen R. This is the first report to describe a mechanism for post-transcriptional regulation of meprin α and will help clarify the role of meprins in the inflammatory response and disease.

• Authors: Alanna N Roff, Ronaldo P Panganiban, Judith S Bond, Faoud T Ishmael
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 7 Pg. 4733-43 (Feb 15 2013) ISSN: 1083-351X [Electronic] United States
• PMID: 23269677 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 3' Untranslated Regions
• ELAV Proteins
• Tristetraprolin
• Metalloendopeptidases
• meprin A

Topics

• 3' Untranslated Regions
• Biotinylation
• Caco-2 Cells
• Down-Regulation
• ELAV Proteins (metabolism)
• Gene Expression Regulation
• Gene Silencing
• Humans
• Inflammation
• Inflammatory Bowel Diseases (metabolism)
• Metalloendopeptidases (metabolism)
• Protein Binding
• RNA Processing, Post-Transcriptional
• Transfection
• Tristetraprolin (metabolism)