ALK-mediated post-transcriptional regulation: focus on RNA-binding proteins

Extensive research has been carried out in the past two decades to provide insights into the molecular mechanisms by which the Nucleophosmin-Anaplastic Lymphoma Kinase (NPM-ALK) exerts its oncogenic effects. These studies led to the concept that NPM-ALK acts at the transcriptional level through the activation of several transcription factors downstream of many different signaling pathways including JAK3/STAT3, PI3K/AKT and RAS/ERK. Nevertheless, the discovery of several RNA-binding proteins (RBPs) within ALK interactome suggested an additional and complementary role of this oncogenic kinase at the post-transcriptional level. This review gives emerging views in ALK-mediated post-transcriptional regulation with a focus on RBPs that are associated with ALK. We will summarize the capacity of NPM-ALK in modulating the biological properties of RBPs and then discuss the role of cytoplasmic aggregates, called AGs for "ALK granules", which are observed in anaplastic large cell lymphoma (ALCL) expressing the ALK kinase. AGs contain polyadenylated mRNAs and numerous RBPs but are distinct from processing bodies (PBs) and stress granules (SGs), two well-known discrete cytoplasmic sites involved in mRNA fate.