title: RNA-binding motif protein 15 binds to the RNA transport element RTE and provides a direct link to the NXF1 export pathway.
abstract: Retroviruses/retroelements provide tools enabling the identification and dissection of basic steps for post-transcriptional regulation of cellular mRNAs. The RNA transport element (RTE) identified in mouse retrotransposons is functionally equivalent to constitutive transport element of Type D retroviruses, yet does not bind directly to the mRNA export receptor NXF1. Here, we report that the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically in vitro and stimulates export and expression of RTE-containing reporter mRNAs in vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus, RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose that RTE evolved as a high affinity RBM15 ligand to provide a splicing-independent link to NXF1, thereby ensuring efficient nuclear export and expression of retrotransposon transcripts.
authors.affiliation: Human Retrovirus Section.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindtner
authors.forename: Andrei S
authors.initials: AS
authors.lastname: Zolotukhin
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Uranishi
authors.forename: Jenifer
authors.initials: J
authors.lastname: Bear
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.forename: Sergey
authors.initials: S
authors.lastname: Smulevitch
authors.forename: Martina
authors.initials: M
authors.lastname: Samiotaki
authors.forename: George
authors.initials: G
authors.lastname: Panayotou
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D012190:Retroviridae / Q000378:metabolism
chemical_list: D008024:Ligands; C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; C431574:RBM15 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012313:RNA