title: Immediate translation of Formin DIAPH1 mRNA after its exiting the nucleus is required for its perinuclear localization in fibroblasts.
abstract: DIAPH1 is a formin protein which promotes actin polymerization, stabilizes microtubules and consequently is involved in cytoskeleton dynamics, cell migration and differentiation. In contrast to the relatively well-understood signaling cascades that regulate DIAPH1 activity, its spatial regulation of biogenesis is not understood. A recent report showed that synthesis of DIAPH1 is confined in the perinuclear ER compartment through translation-dependent mRNA targeting. However, the underlying mechanism of DIAPH1 local synthesis is yet to be elucidated. Here, we provide evidence to demonstrate that the 5'-cap-mediated immediate translation of DIAPH1 mRNA upon exiting nucleus is required for localizing the mRNA in the perinuclear ER compartment. This is supported by data: 1) Delayed translation of DIAPH1 mRNA resulted in loss of perinuclear localization of the mRNA; 2) Once delocalized, DIAPH1 mRNA could not be retargeted to the perinuclear region; and 3) The translation of DIAPH1 mRNA is 5'-cap dependent. These results provide new insights into the novel mechanism of DIAPH1 local synthesis. In addition, these findings have led to the development of new approaches for manipulating DIAPH1 mRNA localization and local protein synthesis in cells for functional studies. Furthermore, a correlation of DIAPH1 mRNA and DIAPH1 protein localization has been demonstrated using a new method to quantify the intracellular distribution of protein.
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York, United States of America.
authors.forename: Guoning
authors.initials: G
authors.lastname: Liao
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002642:Chick Embryo; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005326:Fetal Proteins; D012333:RNA, Messenger