Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs.
The RNA-binding protein IGF2BP1 (IGF-II mRNA binding protein 1) stabilizes the c-myc RNA by associating with the Coding Region instability Determinant (CRD). If and how other proteins cooperate with IGF2BP1 in promoting stabilization of the c-myc mRNA via the CRD remained elusive. Here, we identify various RNA-binding proteins that associate with IGF2BP1 in an RNA-dependent fashion. Four of these proteins (HNRNPU, SYNCRIP, YBX1, and DHX9) were essential to ensure stabilization of the c-myc mRNA via the CRD. These factors associate with IGF2BP1 in a CRD-dependent manner, co-distribute with IGF2BP1 in non-polysomal fractions comprising c-myc mRNA, and colocalize with IGF2BP1 in the cytoplasm. A selective shift of relative c-myc mRNA levels to the polysomal fraction is observed upon IGF2BP1 knockdown. These findings suggest that IGF2BP1 in complex with at least four proteins promotes CRD-mediated mRNA stabilization. Complex formation at the CRD presumably limits the transfer of c-myc mRNA to the polysomal fraction and subsequent translation-coupled decay.
Weidensdorfer
Doreen
D
NBL3-NWG6 ZAMED, Department of Medicine, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
Stöhr
Nadine
N
Baude
Anne
A
Lederer
Marcell
M
Köhn
Marcel
M
Schierhorn
Angelika
A
Buchmeier
Sabine
S
Wahle
Elmar
E
Hüttelmaier
Stefan
S
D001665:Binding Sites; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D014162:Transfection; D051840:Y-Box-Binding Protein 1
D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C406144:IGF2BP1 protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C425312:SYNCRIP protein, human; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human