title: APOBEC3 inhibits DEAD-END function to regulate microRNA activity.
abstract: The RNA binding protein DEAD-END (DND1) is one of the few proteins known to regulate microRNA (miRNA) activity at the level of miRNA-mRNA interaction. DND1 blocks miRNA interaction with the 3'-untranslated region (3'-UTR) of specific mRNAs and restores protein expression. Previously, we showed that the DNA cytosine deaminase, APOBEC3 (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide like 3), interacts with DND1. APOBEC3 has been primarily studied for its role in restricting and inactivating retroviruses and retroelements. In this report, we examine the significance of DND1-APOBEC3 interaction. We found that while human DND1 inhibits miRNA-mediated inhibition of P27, human APOBEC3G is able to counteract this repression and restore miRNA activity. APOBEC3G, by itself, does not affect the 3'-UTR of P27. We found that APOBEC3G also blocks DND1 function to restore miR-372 and miR-206 inhibition through the 3'-UTRs of LATS2 and CX43, respectively. In corollary experiments, we tested whether DND1 affects the viral restriction function or mutator activity of APOBEC3. We found that DND1 does not affect APOBEC3 inhibition of infectivity of exogenous retrovirus HIV (ΔVif) or retrotransposition of MusD. In addition, examination of Ter/Ter;Apobec3-/- mice, lead us to conclude that DND1 does not regulate the mutator activity of APOBEC3 in germ cells. In summary, our results show that APOBEC3 is able to modulate DND1 function to regulate miRNA mediated translational regulation in cells but DND1 does not affect known APOBEC3 function.
authors.affiliation: Department of Genetics, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Ali
authors.forename: Namrata
authors.initials: N
authors.lastname: Karki
authors.forename: Chitralekha
authors.initials: C
authors.lastname: Bhattacharya
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.forename: Donna A
authors.initials: DA
authors.lastname: MacDuff
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stenglein
authors.forename: April J
authors.initials: AJ
authors.lastname: Schumacher
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Demorest
authors.forename: Reuben S
authors.initials: RS
authors.lastname: Harris
authors.forename: Angabin
authors.initials: A
authors.lastname: Matin
authors.forename: Sita
authors.initials: S
authors.lastname: Aggarwal
mesh_terms: D020413:3' Untranslated Regions; D000071480:APOBEC-3G Deaminase; D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D020413:3' Untranslated Regions; C528453:Dnd1 protein, human; C500862:Dnd1 protein, mouse; C546087:MIRN206 microRNA, human; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; C496166:APOBEC3G protein, mouse; D003564:Cytidine Deaminase
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