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Ribosomal proteins L5 and L11 co-operatively inactivate c-Myc via RNA-induced silencing complex

Oncogene volume 33, pages 4916–4923 (2014)Cite this article

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Abstract

Oncogene MYC is highly expressed in many human cancers and functions as a global regulator of ribosome biogenesis. Previously, we reported that ribosomal protein (RP) L11 binds to c-Myc and inhibits its transcriptional activity in response to ribosomal stress. Here, we show that RPL5, co-operatively with RPL11, guides the RNA-induced silencing complex (RISC) to c-Myc mRNA and mediates the degradation of the mRNA, consequently leading to inhibition of c-Myc activity. Knocking down of RPL5 induced c-Myc expression at both mRNA and protein levels, whereas overexpression of RPL5 suppressed c-Myc expression and activity. Immunoprecipitation revealed that RPL5 binds to 3′UTR of c-Myc mRNA and two subunits of RISC, TRBP (HIV-1 TAR RNA-binding protein) and Ago2, mediating the targeting of c-Myc mRNA by miRNAs. Interestingly, RPL5 and RPL11 co-resided on c-Myc mRNA and suppressed c-Myc expression co-operatively. These findings uncover a mechanism by which these two RPs can co-operatively suppress c-Myc expression, allowing a tightly controlled ribosome biogenesis in cells.

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Acknowledgements

We thank Karen Vousden for providing us with the RPL11 mutant plasmid, Mu-shui Dai for offering some reagents and Shelya X Zeng as well as other members of the Lu laboratory for advices and active discussion. This work was supported in part by National Institutes of Health (NIH)-National Cancer Institute (NCI) grants CA095441, CA079721, CA129828 and CA172468 to H.L.

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  1. Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA

    J-M Liao, X Zhou & H Lu

  2. Lady Davis Institute for Medical Research, McGill University AIDS Centre, Montréal, Québec, Canada

    A Gatignol

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  1. J-M Liao
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Correspondence to H Lu.

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Liao, JM., Zhou, X., Gatignol, A. et al. Ribosomal proteins L5 and L11 co-operatively inactivate c-Myc via RNA-induced silencing complex. Oncogene 33, 4916–4923 (2014). https://doi.org/10.1038/onc.2013.430

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