Annexin A2 recognises a specific region in the 3′-UTR of its cognate messenger RNA

Abstract

Annexin A2 is a multifunctional Ca(2+)- and lipid-binding protein. We previously showed that a distinct pool of cellular Annexin A2 associates with mRNP complexes or polysomes associated with the cytoskeleton. Here we report in vitro and in vivo experiments showing that Annexin A2 present in this subset of mRNP complexes interacts with its cognate mRNA and c-myc mRNA, but not with beta(2)-microglobulin mRNA translated on membrane-bound polysomes. The protein recognises sequence elements within the untranslated regions, but not within the coding region, of its cognate mRNA. Alignment of the Annexin A2-binding 3'-untranslated regions of annexin A2 mRNA from several species reveals a five nucleotide consensus sequence 5'-AA(C/G)(A/U)G. The Annexin A2-interacting region of the 3'-untranslated region can be mapped to a sequence of about 100 nucleotides containing two repeats of the consensus sequence. The binding elements appear to involve both single and double stranded regions, indicating that a specific higher order mRNA structure is required for binding to Annexin A2. We suggest that this type of interaction is representative for a group of mRNAs translated on cytoskeleton-bound polysomes.

Annexin A2 Reduces PCSK9 Protein Levels via a Translational Mechanism and Interacts with the M1 and M2 Domains of PCSK9

“…Therefore, it is possible that AnxA2 plays a role in both localization and/or activation/repression of translation during transport of specific mRNAs, including that of PCSK9. Trans-acting proteins on 3ЈUTR mainly regulate mRNA transport or their stability, whereas those interacting with the 5ЈUTR are mostly involved in initiation of translation (45). Based on RIP assay results, endogenous PCSK9 mRNA in Huh7 cells is coimmunoprecipitated with AnxA2, which supports the hypothesis of PCSK9 regulation through AnxA2 binding with PCSK9 mRNA.…”

“…These studies identified and suggested a consensus motif 5Ј-AA(C/G)(A/U)G-3Ј that was frequently present in mRNA regions binding AnxA2. AnxA2 is also associated with a subpopulation of messenger ribonucleoprotein complexes (46) and can reduce its own translation (45). Therefore, it is possible that AnxA2 plays a role in both localization and/or activation/repression of translation during transport of specific mRNAs, including that of PCSK9.…”

“…Therefore, AnxA2 clearly forms a com- plex with the 3ЈUTR of PCSK9 mRNA. Future experiments will be required to confirm whether AnxA2 binds to one or more site(s) in the 3ЈUTR of PCSK9 mRNA to inhibit its translation, as it does for its own translation (45). Furthermore, AnxA2 may also inhibit PCSK9 mRNA transport and/or reduce its stability.…”

Dynamic reciprocity: the role of annexin A2 in tissue integrity

“…Here annexin A2 functions as a transporter of particular transcription factors and mRNA, to and from the nucleus, respectively (Hollas et al, 2006). In addition, annexin A2 nuclear translocation has been identified as a protective mechanism against DNA-damage (Madureira et al, 2012).…”

Analysis of Turnover and Translation Regulatory RNA-Binding Protein Expression through Binding to Cognate mRNAs

“…Similar self-regulatory schemes have been reported for several other RBPs, such as hnRNP M, the sex-lethal protein Sxl, and tra2-␤1; these RBPs bind to their respective cognate pre-mRNAs and influence their splicing (8,21,50). Examples other than splicing factors include the RBP annexin A2, which associates with its cognate mRNA and was proposed to influence its translation (23). Among conventional TTR-RBPs, TTP was shown to bind to and promote the decay of the TTP mRNA, providing a distinct example of a posttranscriptional negative-feedback loop in this protein family (52).…”