Interaction with 14-3-3 adaptors regulates the sorting of hMex-3B RNA-binding protein to distinct classes of RNA granules.
Stress granules (SG) and processing bodies (PBs) are cytoplasmic ribonucleoprotein particles whose assembly is induced by different stimuli. SG are the site of storage of untranslated transcripts formed in response to environmental stress, whereas PBs are involved in mRNA turnover. We recently characterized a novel family of four human proteins related to the Caenorhabditis elegans Mex-3, a RNA binding protein involved in the establishment of the anterior-posterior embryonic asymmetry and in the maintenance of germline pluripotency. We now report that the adaptor proteins 14-3-3 bind to hMex-3B but not to the three other hMex-3 family members. Serine 462, when phosphorylated, is the major 14-3-3 docking site on hMex-3B, and manipulation of this interaction reveals that 14-3-3 both stabilizes hMex-3B and modulates its ability to bind RNA. Furthermore, the complex formed between hMex-3B and Argonaute proteins is excluded from PBs when the interaction with 14-3-3 is disrupted, whereas the recruitment to SG is not affected. Thus, 14-3-3 exerts combined effects on hMex-3B and acts as a major regulator of the sorting between distinct classes of RNA granules.
Courchet
Julien
J
CNRS UMR5201, Laboratoire de Génétique Moléculaire, Signalisation et Cancer, Lyon F-69008, France.
Buchet-Poyau
Karine
K
Potemski
Auriane
A
Brès
Aurélie
A
Jariel-Encontre
Isabelle
I
Billaud
Marc
M
D048948:14-3-3 Proteins / Q000378:metabolism*; D060565:Argonaute Proteins; D002460:Cell Line; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D055550:Protein Stability; D012313:RNA / Q000145:classification / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D048948:14-3-3 Proteins; C115848:AGO1 protein, human; D060565:Argonaute Proteins; D039642:Eukaryotic Initiation Factors; C519163:MEX3B protein, human; D016601:RNA-Binding Proteins; D012313:RNA