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A Novel Function of Tis11b/BRF1 As a Regulator of Dll4 MRNA 3'-end Processing

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Journal Mol Biol Cell
Date 2011 Aug 12
PMID 21832157
Citations 10
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Abstract

Tis11b/BRF1 belongs to the tristetraprolin family, the members of which are involved in AU-rich-dependent regulation of mRNA stability/degradation. Mouse inactivation of the Tis11b gene has revealed disorganization of the vascular network and up-regulation of the proangiogenic factor VEGF. However, the VEGF deregulation alone cannot explain the phenotype of Tis11b knockouts. Therefore we investigated the role of Tis11b in expression of Dll4, another angiogenic gene for which haploinsufficiency is lethal. In this paper, we show that Tis11b silencing in endothelial cells leads to up-regulation of Dll4 protein and mRNA expressions, indicating that Dll4 is a physiological target of Tis11b. Tis11b protein binds to endogenous Dll4 mRNA, and represses mRNA expression without affecting its stability. In the Dll4 mRNA 3' untranslated region, we identified one particular AUUUA motif embedded in a weak noncanonical polyadenylation (poly(A)) signal as the major Tis11b-binding site. Moreover, we observed that inhibition of Tis11b expression changes the ratio between mRNAs that are cleaved or read through at the poly(A) signal position, suggesting that Tis11b can interfere with mRNA cleavage and poly(A) efficiency. Last, we report that this Tis11b-mediated mechanism is used by endothelial cells under hypoxia for controlling Dll4 mRNA levels. This work constitutes the first description of a new function for Tis11b in mammalian cell mRNA 3'-end maturation.

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References
1.
Phillips R, Ramos S, Blackshear P . Members of the tristetraprolin family of tandem CCCH zinc finger proteins exhibit CRM1-dependent nucleocytoplasmic shuttling. J Biol Chem. 2002; 277(13):11606-13. DOI: 10.1074/jbc.M111457200. View

2.
Cherradi N, Lejczak C, Desroches-Castan A, Feige J . Antagonistic functions of tetradecanoyl phorbol acetate-inducible-sequence 11b and HuR in the hormonal regulation of vascular endothelial growth factor messenger ribonucleic acid stability by adrenocorticotropin. Mol Endocrinol. 2005; 20(4):916-30. PMC: 2214857. DOI: 10.1210/me.2005-0121. View

3.
Hellstrom M, Phng L, Gerhardt H . VEGF and Notch signaling: the yin and yang of angiogenic sprouting. Cell Adh Migr. 2009; 1(3):133-6. PMC: 2634014. DOI: 10.4161/cam.1.3.4978. View

4.
Milligan L, Torchet C, Allmang C, Shipman T, Tollervey D . A nuclear surveillance pathway for mRNAs with defective polyadenylation. Mol Cell Biol. 2005; 25(22):9996-10004. PMC: 1280253. DOI: 10.1128/MCB.25.22.9996-10004.2005. View

5.
Baou M, Jewell A, Murphy J . TIS11 family proteins and their roles in posttranscriptional gene regulation. J Biomed Biotechnol. 2009; 2009:634520. PMC: 2722025. DOI: 10.1155/2009/634520. View