Affiliation:
1. Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University, Belfast BT9 7BL, United Kingdom
2. The Patrick G Johnston Centre for Cancer Research, Queen’s University, Belfast BT9 7BL, United Kingdom
Abstract
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.
Funder
Wellcome Trust
UKRI | Biotechnology and Biological Sciences Research Council
Publisher
Proceedings of the National Academy of Sciences