ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5'UTR.
p27Kip1 restrains cell proliferation by binding to and inhibiting cyclin-dependent kinases. To investigate the mechanisms of p27 translational regulation, we isolated a complete p27 cDNA and identified an internal ribosomal entry site (IRES) located in its 5'UTR. The IRES allows for efficient p27 translation under conditions where cap-dependent translation is reduced. Searching for possible regulators of IRES activity we have identified the neuronal ELAV protein HuD as a specific binding factor of the p27 5'UTR. Increased expression of HuD or the ubiquitously expressed HuR protein specifically inhibits p27 translation and p27 IRES activity. Consistent with an inhibitory role of Hu proteins in p27 translation, siRNA mediated knockdown of HuR induced endogenous p27 protein levels as well as IRES-mediated reporter translation and leads to cell cycle arrest in G1.
Kullmann
Michael
M
Max-Planck-Institute of Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Göpfert
Ulrich
U
Siewe
Basile
B
Hengst
Ludger
L
D020121:5' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D051959:ELAV Proteins; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D020121:5' Untranslated Regions; D051959:ELAV Proteins; D018809:Proliferating Cell Nuclear Antigen; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C413374:p27 antigen