The RNA-binding motif protein 15B (RBM15B/OTT3) acts as cofactor of the nuclear export receptor NXF1.
The human SPEN family proteins SHARP, RBM15/OTT1, and RBM15B/OTT3 share the structural domain architecture but show distinct functional properties. Here, we examined the function of OTT3 and compared it with its paralogues RBM15 and SHARP. We found that OTT3, like RBM15, has post-transcriptional regulatory activity, whereas SHARP does not, supporting a divergent role of RBM15 and OTT3. OTT3 shares with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Mutational analysis revealed direct interaction of OTT3 and RBM15 with NXF1 via their C-terminal regions. Biochemical and subcellular localization studies showed that OTT3 and RBM15 also interact with each other in vivo, further supporting a shared function. Genetic knockdown of RBM15 in mouse is embryonically lethal, indicating that OTT3 cannot compensate for the RBM15 loss, which supports the notion that these proteins, in addition to sharing similar activities, likely have distinct biological roles.
Uranishi
Hiroaki
H
Human Retrovirus Section, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702-1201, USA.
Zolotukhin
Andrei S
AS
Lindtner
Susan
S
Warming
Soren
S
Zhang
Gen-Mu
GM
Bear
Jenifer
J
Copeland
Neal G
NG
Jenkins
Nancy A
NA
Pavlakis
George N
GN
Felber
Barbara K
BK
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D040681:Structural Homology, Protein
C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; C431574:RBM15 protein, human; C546581:RBM15B protein, human; D016601:RNA-Binding Proteins; C519408:Rbm15 protein, mouse