p16INK4a translation suppressed by miR-24

Ashish Lal, Hyeon Ho Kim, Kotb Abdelmohsen, Yuki Kuwano, Rudolf Pullmann, Subramanya Srikantan, Ramesh Subrahmanyam, Jennifer L. Martindale, Xiaoling Yang, Fariyal Ahmed, Francisco Navarro, Derek M Dykxhoorn, Judy Lieberman, Myriam Gorospe

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

Background: Expression of the tumor suppressor p16INK4a increases during aging and replicative senescence. Methodology/principal findings: 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/significance: Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation.

Original languageEnglish
Article numbere1864
JournalPLoS One
Volume3
Issue number3
DOIs
StatePublished - Mar 26 2008
Externally publishedYes

Fingerprint

Cell Aging
MicroRNAs
microRNA
translation (genetics)
Bearings (structural)
Messenger RNA
uterine cervical neoplasms
3' Untranslated Regions
3' untranslated regions
Fibroblasts
Diploidy
fibroblasts
Tumors
Elongation
Proteins
diploidy
proteins
Aging of materials
Cells
Carcinoma

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lal, A., Kim, H. H., Abdelmohsen, K., Kuwano, Y., Pullmann, R., Srikantan, S., ... Gorospe, M. (2008). p16INK4a translation suppressed by miR-24. PLoS One, 3(3), [e1864]. https://doi.org/10.1371/journal.pone.0001864

p16INK4a translation suppressed by miR-24. / Lal, Ashish; Kim, Hyeon Ho; Abdelmohsen, Kotb; Kuwano, Yuki; Pullmann, Rudolf; Srikantan, Subramanya; Subrahmanyam, Ramesh; Martindale, Jennifer L.; Yang, Xiaoling; Ahmed, Fariyal; Navarro, Francisco; Dykxhoorn, Derek M; Lieberman, Judy; Gorospe, Myriam.

In: PLoS One, Vol. 3, No. 3, e1864, 26.03.2008.

Research output: Contribution to journalArticle

Lal, A, Kim, HH, Abdelmohsen, K, Kuwano, Y, Pullmann, R, Srikantan, S, Subrahmanyam, R, Martindale, JL, Yang, X, Ahmed, F, Navarro, F, Dykxhoorn, DM, Lieberman, J & Gorospe, M 2008, 'p16INK4a translation suppressed by miR-24', PLoS One, vol. 3, no. 3, e1864. https://doi.org/10.1371/journal.pone.0001864
Lal A, Kim HH, Abdelmohsen K, Kuwano Y, Pullmann R, Srikantan S et al. p16INK4a translation suppressed by miR-24. PLoS One. 2008 Mar 26;3(3). e1864. https://doi.org/10.1371/journal.pone.0001864
Lal, Ashish ; Kim, Hyeon Ho ; Abdelmohsen, Kotb ; Kuwano, Yuki ; Pullmann, Rudolf ; Srikantan, Subramanya ; Subrahmanyam, Ramesh ; Martindale, Jennifer L. ; Yang, Xiaoling ; Ahmed, Fariyal ; Navarro, Francisco ; Dykxhoorn, Derek M ; Lieberman, Judy ; Gorospe, Myriam. / p16INK4a translation suppressed by miR-24. In: PLoS One. 2008 ; Vol. 3, No. 3.
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AU - Srikantan, Subramanya

AU - Subrahmanyam, Ramesh

AU - Martindale, Jennifer L.

AU - Yang, Xiaoling

AU - Ahmed, Fariyal

AU - Navarro, Francisco

AU - Dykxhoorn, Derek M

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AU - Gorospe, Myriam

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AB - Background: Expression of the tumor suppressor p16INK4a increases during aging and replicative senescence. Methodology/principal findings: 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/significance: Together, our results suggest that miR-24 represses the initiation and elongation phases of p16 translation.

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