The mRNA-binding Site of Annexin A2 Resides in Helices C–D of its Domain IV

Aukrust, Ingvild; Hollås, Hanne; Strand, Elin; Evensen, Lasse; Travé, Gilles; Flatmark, Torgeir; Vedeler, Anni

doi:10.1016/j.jmb.2007.02.094

Cited by 33 publications

(58 citation statements)

References 51 publications

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“…Annexin A2 (ANXA2) is an RNA-binding protein (Aukrust et al, 2007; Filipenko et al, 2004) that plays a key role in membrane vesicle trafficking and MVB biogenesis (Gerke et al, 2005; Mayran et al, 2003; Morel et al, 2009). Interestingly, recent reports indicate that ANXA2 is recruited to HCV replication sites where it regulates virus particle production (Backes et al, 2010; Saxena et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Short-Range Exosomal Transfer of Viral RNA from Infected Cells to Plasmacytoid Dendritic Cells Triggers Innate Immunity

Dreux

Garaigorta

Boyd

et al. 2012

Cell Host & Microbe

416

450

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Summary Viral nucleic acids often trigger an innate immune response in infected cells. Many viruses, including hepatitis C virus (HCV), have evolved mechanisms to evade intracellular recognition. Nevertheless, HCV-permissive cells can trigger a viral RNA-, TLR7- and cell contact-dependent compensatory interferon response in nonpermissive plasmacytoid dendritic cells (pDCs). Here we report that these events are mediated by transfer of HCV RNA-containing exosomes from infected cells to pDCs. The exosomal viral RNA transfer is dependent on the endosomal sorting complex (ESCRT) machinery and on Annexin A2, an RNA-binding protein involved in membrane vesicle trafficking, and it is suppressed by exosome release inhibitors. Further, purified concentrated HCV RNA-containing exosomes are sufficient to activate pDCs. Thus, vesicular sequestration and exosomal export of viral RNA may serve both as a viral strategy to evade pathogen-sensing within infected cells and as a host strategy to induce an unopposed innate response in replication-nonpermissive by-stander cells.

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Section: Resultsmentioning

confidence: 99%

Short-Range Exosomal Transfer of Viral RNA from Infected Cells to Plasmacytoid Dendritic Cells Triggers Innate Immunity

Dreux

Garaigorta

Boyd

et al. 2012

Cell Host & Microbe

416

450

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“…Indeed, it has been reported that ANXA2 has the ability to be associated with several proteins such as p11 and tPA [26,27]. Moreover, ANXA2 can bind directly to both mRNA and ribonucleotide homopolymers [28,29]. Thus, there is a possibility that ANXA2 recruits miRNAs via its interaction with other miRNA-associated proteins.…”

Section: Discussionmentioning

confidence: 99%

Commitment of Annexin A2 in recruitment of microRNAs into extracellular vesicles

Hagiwara

Katsuda²,

Gailhouste³

et al. 2015

FEBS Letters

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a b s t r a c tExtracellular vesicles (EVs) contain microRNAs (miRNAs). However, the exact molecular mechanisms of the recruitment of miRNAs in EVs are not well characterized. Based on proteomic analysis, we identified that silencing of Annexin A2 (ANXA2) significantly decreased the amount of miRNAs in EVs. In addition, microarray analysis revealed that ANXA2 regulated the loading of miRNAs into EVs in a sequence independent manner. Lastly, immunoprecipitation analysis confirmed that ANXA2 could bind miRNAs in EVs in the presence of Ca 2+ . These observations demonstrate that ANXA2 plays an important role in the packaging process of miRNAs into EVs.

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“…Interestingly, this mRNA binding function was observed only for monomeric annexin A2. By mapping the mRNA binding site of annexin A2 to the helices C-D in its domain IV, Vedeler’s group recognized that this motif is unique among the previously identified RNA binding motifs (such as the RNP motif, the arginine-rich motif, the RGG box, the KH motif, the double stranded RNA-binding motif, and the zinc finger-knuckle motif) [146]. Specifically, the positively charged polar residues in this domain that are easily accessible and solvent exposed are involved in RNA binding.…”

Section: Functions Of Annexin A2mentioning

confidence: 99%

“…The initial interactions with RNA are suggested to be non-specific electrostatic interactions between lysine residues in annexin A2 and the negatively charged phosphate residues in the mRNA backbone. Further stabilization of the interaction is promoted by the conformation change in annexin A2 upon to calcium-binding [103,146]. The annexin A2 binding site on the mRNA of c-myc and annexin A2 involves an 80–100 nucleotide sequence in the 3′-UTR region of the mRNA.…”

Section: Functions Of Annexin A2mentioning

confidence: 99%

Annexin A2 Heterotetramer: Structure and Function

Bharadwaj

Bydoun

Holloway

et al. 2013

IJMS

236

346

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Annexin A2 is a pleiotropic calcium- and anionic phospholipid-binding protein that exists as a monomer and as a heterotetrameric complex with the plasminogen receptor protein, S100A10. Annexin A2 has been proposed to play a key role in many processes including exocytosis, endocytosis, membrane organization, ion channel conductance, and also to link F-actin cytoskeleton to the plasma membrane. Despite an impressive list of potential binding partners and regulatory activities, it was somewhat unexpected that the annexin A2-null mouse should show a relatively benign phenotype. Studies with the annexin A2-null mouse have suggested important functions for annexin A2 and the heterotetramer in fibrinolysis, in the regulation of the LDL receptor and in cellular redox regulation. However, the demonstration that depletion of annexin A2 causes the depletion of several other proteins including S100A10, fascin and affects the expression of at least sixty-one genes has confounded the reports of its function. In this review we will discuss the annexin A2 structure and function and its proposed physiological and pathological roles.

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The mRNA-binding Site of Annexin A2 Resides in Helices C–D of its Domain IV

Cited by 33 publications

References 51 publications

Short-Range Exosomal Transfer of Viral RNA from Infected Cells to Plasmacytoid Dendritic Cells Triggers Innate Immunity

Short-Range Exosomal Transfer of Viral RNA from Infected Cells to Plasmacytoid Dendritic Cells Triggers Innate Immunity

Commitment of Annexin A2 in recruitment of microRNAs into extracellular vesicles

Annexin A2 Heterotetramer: Structure and Function

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