RNA-binding IMPs promote cell adhesion and invadopodia formation.
Oncofetal RNA-binding IMPs have been implicated in mRNA localization, nuclear export, turnover and translational control. To depict the cellular actions of IMPs, we performed a loss-of-function analysis, which showed that IMPs are necessary for proper cell adhesion, cytoplasmic spreading and invadopodia formation. Loss of IMPs was associated with a coordinate downregulation of mRNAs encoding extracellular matrix and adhesion proteins. The transcripts were present in IMP RNP granules, implying that IMPs were directly involved in the post-transcriptional control of the transcripts. In particular, we show that a 5.0 kb CD44 mRNA contained multiple IMP-binding sites in its 3'UTR, and following IMP depletion this species became unstable. Direct knockdown of the CD44 transcript mimicked the effect of IMPs on invadopodia, and we infer that CD44 mRNA stabilization may be involved in IMP-mediated invadopodia formation. Taken together, our results indicate that RNA-binding proteins exert profound effects on cellular adhesion and invasion during development and cancer formation.
Vikesaa
Jonas
J
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Hansen
Thomas V O
TV
Jønson
Lars
L
Borup
Rehannah
R
Wewer
Ulla M
UM
Christiansen
Jan
J
Nielsen
Finn C
FC
D020413:3' Untranslated Regions; D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D018960:Hyaluronan Receptors; C406144:IGF2BP1 protein, human; C498780:IGF2BP3 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins