RNA-binding motif protein 4 translocates to cytoplasmic granules and suppresses translation via argonaute2 during muscle cell differentiation.
The RNA-binding motif protein 4 (RBM4) plays multiple roles in mRNA metabolism, including translation control. RBM4 suppresses cap-dependent translation but activates internal ribosome entry site-mediated translation. Because of its high expression level in muscle and heart, we investigated the function of RBM4 in myoblast cells. Here, we demonstrate that RBM4 is phosphorylated and translocates to the cytoplasm in mouse C2C12 cells upon cell differentiation. Notably, RBM4 is transiently deposited into cytoplasmic granules containing microtubule assembly factors as well as poly(A)(+) RNAs. Moreover, RBM4 colocalizes with the components of micro-ribonucleoproteins, including the Argonaute2 (Ago2) protein, during muscle cell differentiation. RBM4 interacts directly with Ago2 and may recruit Ago2 to suppress translation of target mRNAs. Furthermore, RBM4 selectively associates with muscle cell-specific microRNAs and potentiates their translation repression activity by promoting micro-ribonucleoprotein association with target mRNAs. Altogether, our results suggest that RBM4 translocates to the cytoplasm and participates in translation suppression during muscle cell differentiation.
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Jung-Chun
JC
Lin
Woan-Yuh
WY
Tarn
D000818:Animals; D060565:Argonaute Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000502:physiology; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C466422:AGO2 protein, human; D060565:Argonaute Proteins; C530105:Ccnd1 protein, mouse; D015852:Eukaryotic Initiation Factor-2; D035683:MicroRNAs; C473692:RBM4 protein, human; D016601:RNA-Binding Proteins; D019938:Cyclin D1