Multiple Roles of Annexin A2 in Post-Transcriptional Regulation of Gene Expressio

Abstract

Increasing evidence points to the participation of the multifunctional protein Annexin A2 (AnxA2) in mRNA localisation as well as the translation of certain mRNAs on cytoskeleton-bound polysomes, and thereby in the regulation of the biosynthesis of specific proteins, such as c-Myc and AnxA2 itself, which are linked to cellular transformation. AnxA2 is most likely activated by signalling pathways, which result in its post-translational modifications and modulate its binding to various ligands, including specific mRNAs. Positive and polar residues in helices C-D in domain IV of AnxA2 bind to cis-acting elements in the 3'-UTRs of its cognate, c-myc, collagen prolyl 4-hydroxylase-α(I) and N-methyl-D-aspartate R1 mRNAs, thus contributing to post-transcriptional regulation of the expression of specific genes. The cis-acting elements appear to constitute a higher order structure, frequently containing the consensus sequence 5'-AA(C/G)(A/U)G; however, non-canonical AnxA2 binding sites may also be involved. In the case of c-myc mRNA, the association with AnxA2 appears to regulate its localisation and translation. In addition, the binding of AnxA2 to a pseudoknot structure present in infectious bronchitis viral RNA results in reduced efficiency of -1 ribosomal frameshifting, indicating its recruitment as a host protein during viral infection. Finally, the association of AnxA2 with endosomes and exosomes suggests a role in co-ordinated transport of mRNA and vesicles, i.e. processes that respond to extracellular signals and are expected to employ multifunctional proteins.