A role for hnRNP C1/C2 and Unr in internal initiation of translation during mitosis.
The upstream of N-Ras (Unr) protein is involved in translational regulation of specific genes. For example, the Unr protein contributes to translation mediated by several viral and cellular internal ribosome entry sites (IRESs), including the PITSLRE IRES, which is activated at mitosis. Previously, we have shown that translation of the Unr mRNA itself can be initiated through an IRES. Here, we show that UNR mRNA translation and UNR IRES activity are significantly increased during mitosis. Functional analysis identified hnRNP C1/C2 proteins as UNR IRES stimulatory factors, whereas both polypyrimidine tract-binding protein (PTB) and Unr were found to function as inhibitors of UNR IRES-mediated translation. The increased UNR IRES activity during mitosis results from enhanced binding of the stimulatory hnRNP C1/C2 proteins and concomitant dissociation of PTB and Unr from the UNR IRES RNA. Our data suggest the existence of an IRES-dependent cascade in mitosis comprising hnRNP C1/C2 proteins that stimulate Unr expression, and Unr, in turn, contributes to PITSLRE IRES activity. The observation that RNA interference-mediated knockdown of hnRNP C1/C2 and Unr, respectively, abrogates and retards mitosis points out that regulation of IRES-mediated translation by hnRNP C1/C2 and Unr might be important in mitosis.
Schepens
Bert
B
Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, VIB-Ghent University, Gent-Zwijnaarde, Belgium.
Tinton
Sandrine A
SA
Bruynooghe
Yanik
Y
Parthoens
Eef
E
Haegman
Mira
M
Beyaert
Rudi
R
Cornelis
Sigrid
S
D002455:Cell Division; D002460:Cell Line; D002846:Chromatography, Affinity; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D016195:G2 Phase; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D008957:Models, Genetic; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D013997:Time Factors
C439788:C1 HNRNP; C079950:CSDE1 protein, human; D004268:DNA-Binding Proteins; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D016601:RNA-Binding Proteins; C447612:CDK11a protein, human; D018844:Cyclin-Dependent Kinases