p16(INK4a) translation suppressed by miR-24.
BACKGROUND
Expression of the tumor suppressor p16(INK4a) increases during aging and replicative senescence.


RESULTS
Here, we report that the microRNA miR-24 suppresses p16 expression in human diploid fibroblasts and cervical carcinoma cells. Increased p16 expression with replicative senescence was associated with decreased levels of miR-24, a microRNA that was predicted to associate with the p16 mRNA coding and 3'-untranslated regions. Ectopic miR-24 overexpression reduced p16 protein but not p16 mRNA levels. Conversely, introduction of antisense (AS)-miR-24 blocked miR-24 expression and markedly enhanced p16 protein levels, p16 translation, and the production of EGFP-p16 reporter bearing the miR-24 target recognition sites.


CONCLUSIONS
Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation.
Lal
Ashish
A
Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, Maryland, United States of America. alal@cbrinstitute.org
Kim
Hyeon Ho
HH
Abdelmohsen
Kotb
K
Kuwano
Yuki
Y
Pullmann
Rudolf
R
Srikantan
Subramanya
S
Subrahmanyam
Ramesh
R
Martindale
Jennifer L
JL
Yang
Xiaoling
X
Ahmed
Fariyal
F
Navarro
Francisco
F
Dykxhoorn
Derek
D
Lieberman
Judy
J
Gorospe
Myriam
M
D001483:Base Sequence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D014176:Protein Biosynthesis
D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D035683:MicroRNAs