Aberrant regulation of mRNA 3' untranslated region in cancers and inflammation

Mai Eva Nguyen Chi, Dominique Morello

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Almost 10 of mammalian coding mRNAs contain in their 3 untranslated region a sequence rich in adenine and uridine residues known as AU-rich element (ARE). Many of them encode oncogenes (for instance c-Myc and c-Fos), cell cycle regulators (cyclin D1, A1, B1), cytokines (TNFalpha, IL2) and growth factors (GM-CSF) which are overexpressed in cancer or inflammatory diseases due to increased mRNA stability and/or translation. AREs are recognized by a group of proteins, collectively called AUBPs which display various functions. For instance, HuR/ELAV is mainly known to protect ARE-containing mRNAs from degradation, while AUF1, TTP and KSRP act to destabilize their bound target mRNAs and TIA/TIAR to inhibit their translation. Alterations in ARE sequences or AUBP abundance, cellular localization or activity due to post-translational modifications such as phosphorylation can promote or enhance malignancy or perturb immune homeostasis. Here, c-myc and TNFalpha are chosen as examples to illustrate how altered 3 UTR gene regulation impacts on pathologies.
Original languageEnglish
Pages (from-to)290 - 296
Number of pages7
JournalMedecine sciences : M/S
Volume24
Issue number3
Publication statusPublished - 2008
Externally publishedYes

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