AUF1/hnRNP D represses expression of VEGF in macrophages

Abstract

Vascular endothelial growth factor (VEGF) expression is regulated by sequence elements in the 3′ UTR of VEGF mRNA. AUF1/hnRNP D suppresses VEGF 3′ UTR–dependent expression. Peptides with arginine–glycine–glycine motifs derived from AUF1 also suppress VEGF expression.

Antagonistic Function of the RNA-binding Protein HuR and miR-200b in Post-transcriptional Regulation of Vascular Endothelial Growth Factor-A Expression and Angiogenesis

“…Although the Vegf-a gene is strongly induced by hypoxia and cytokines at the level of transcription, it is also regulated at the post-transcriptional level by RNA-binding proteins and miRNAs such as AUF, hnRNP L, miR-15b, 16, and 20a/b (24,26,43). HuR is known to bind directly to Vegf-a mRNA (Fig.…”

“…The Vegf-a 3Ј-UTR contains several important cis-acting elements, including CA-rich element, IFN-␥-activated inhibitor of translation element (GAIT), and ARE, and is regulated by its RBPs such as AUF, tristetraprolin, heterogeneous nuclear ribonucleoprotein (hnRNP L) and HuR (21)(22)(23)(24)(25). ARE-binding proteins such as AUF and tristetraprolin destabilize Vegf-a mRNA in macrophage and tumor cells, respectively (24,25). Furthermore, hnRNP L and the GAIT complex regulate VEGF-A expression in a mutually exclusive, stimulus-dependent manner through an RNA conformational change known as riboswitch (26).…”

AUF-1 and YB-1 independently regulate β-globin mRNA in developing erythroid cells through interactions with poly(A)-binding protein

“…This mRNP, which we term the ‘β-complex’, is cytoplasm-restricted and erythroidspecific, suggesting that it participates in regulating β-globin mRNA at the stages of erythroid differentiation when progenitor cells are transcriptionally silenced and, subsequently, extrude their nuclei. Several well-described properties of AUF-1 and YB-1 are consistent with this possibility: both proteins express at high levels in late erythropoiesis (van Zalen et al, 2012), display mRNA-stabilizing activities (Capowski et al, 2001; Fellows et al, 2012; McGray et al, 2011), and interact with poly(A) binding protein (PABP) (Higashi et al, 2011; Laroia et al, 1999), a factor that enhances the half-lives of heterologous mRNAs by maintaining the integrities of their polyadenylate tails (Bernstein et al, 1989; Wilusz et al, 2001). …”

“…The cytoplasm-restricted assembly of the β-complex (van Zalen et al, 2012) and the known RNA-regulatory properties of its constituent trans -acting factors (Capowski et al, 2001; Fellows et al, 2012; McGray et al, 2011) predict that the mRNP participates in post-transcriptional processes affecting the stability and/or the translational efficiency of mature β-globin mRNA. Our previous studies demonstrated a significant defect in the accumulation of β-globin mRNA when the integrities of either the cis - or the trans -acting elements of the β-complex were interrupted (Jiang et al, 2006; van Zalen et al, 2012), suggesting that the β-complex is integral to β-globin post-transcriptional regulatory mechanisms.…”

“…For example, AUF-1 and YB-1 bind simultaneously to a synthetic AU-rich RNA (Moraes et al, 2003), consistent with their inclusion in a functional multiprotein mRNP (Skalweit et al, 2003). In contrast, AUF-1 and YB-1 bind independently to defined mRNA-stability motifs in the 3′UTRs of mRNAs that encode GMCSF, VEGF, and TSP-1 (Capowski et al, 2001; Fellows et al, 2012; McGray et al, 2011), illustrating the capacities of these regulatory factors for structural and functional independence. A more comprehensive description of the mechanism(s) through which AUF-1 and YB-1 regulate β-globin mRNA, as either heteromeric or monomeric mRNPs, is fundamental to understanding the post-transcriptional processes that are required for normal erythropoiesis.…”