The scaffolding protein AKAP12 regulates mRNA localization and translation.

Regulation of subcellular messenger (m)RNA localization is a fundamental biological mechanism, which adds a spatial dimension to the diverse layers of post-transcriptional control of gene expression. The cellular compartment in which mRNAs are located may define distinct aspects of the encoded proteins, ranging from production rate and complex formation to localized activity. Despite the detailed roles of localized mRNAs that have emerged over the past decades, the identity of factors anchoring mRNAs to subcellular domains remains ill-defined. Here, we used an unbiased method to profile the RNA-bound proteome in migrating endothelial cells (ECs) and discovered that the plasma membrane (PM)-associated scaffolding protein A-kinase anchor protein (AKAP)12 interacts with various mRNAs, including transcripts encoding kinases with Actin remodeling activity. In particular, AKAP12 targets a transcript coding for the kinase Abelson Tyrosine-Protein Kinase 2 (ABL2), which we found to be necessary for adequate filopodia formation and angiogenic sprouting. Moreover, we demonstrate that AKAP12 is necessary for anchoring ABL2 mRNA to the PM and show that in the absence of AKAP12, the translation efficiency of ABL2 mRNA is reduced. Altogether, our work identified a unique post-transcriptional function for AKAP12 and sheds light into mechanisms of spatial control of gene expression.

RNA-binding proteins and translation control in angiogenesis.

Tissue vascularization through the process of angiogenesis ensures adequate oxygen and nutrient supply during development and regeneration. The complex morphogenetic events involved in new blood vessel formation are orchestrated by a tightly regulated crosstalk between extra and intracellular factors. In this context, RNA-binding protein (RBP) activity and protein translation play fundamental roles during the cellular responses triggered by particular environmental cues. A solid body of work has demonstrated that key RBPs (such as HuR, TIS11 proteins, hnRNPs, NF90, QKIs and YB1) are implicated in both physiological and pathological angiogenesis. These RBPs are critical for the metabolism of messenger (m)RNAs encoding angiogenic modulators and, importantly, strong evidence suggests that RBP-mRNA interactions can be altered in disease. Lesser known, but not less important, the mechanistic aspects of protein synthesis can also regulate the generation of new vessels. In this review, we outline the key findings demonstrating the implications of RBP-mediated RNA regulation and translation control in angiogenesis. Furthermore, we highlight how these mechanisms of post-transcriptional control of gene expression have led to promising therapeutic strategies aimed at targeting undesired blood vessel formation.