Transfer-RNA-mediated enhancement of ribosomal proteins S6 kinases signaling for cell proliferation

Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun Shin Lee, Hyeong Gon Moon, Sunghoon Kim

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8 Citations (Scopus)

Abstract

While transfer-RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNALeu overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNALeu and was independent to mTOR (mammalian target of rapamycin) signaling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNALeu overexpression. Through SILAC (stable isotope labeling by/with amino acids in cell culture) and combined mass spectrometry analysis, we identified EBP1 (ErbB3-binding protein 1) as the tRNALeu-binding protein. We suspected that the overexpression of free tRNALeu would reinforce ErbB2/ErbB3 signaling pathway by disturbing the interaction between ErbB3 and EBP1, resulting in RSK1/MSK2 phosphorylation, improving cell proliferation and resistance to death. Analysis of samples from patients with breast cancer also indicated an association between tRNALeu overexpression and the ErbB2-positive population. Our results suggested a possible link between tRNALeu overexpression and RSK1/MSK2 activation and ErbB2/ErbB3 signaling.

Original languageEnglish
Pages (from-to)635-648
Number of pages14
JournalRNA Biology
Volume15
Issue number4-5
DOIs
Publication statusPublished - 2018 May 4

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Kwon, N. H., Lee, M. R., Kong, J., Park, S. K., Hwang, B. J., Kim, B. G., Lee, E. S., Moon, H. G., & Kim, S. (2018). Transfer-RNA-mediated enhancement of ribosomal proteins S6 kinases signaling for cell proliferation. RNA Biology, 15(4-5), 635-648. https://doi.org/10.1080/15476286.2017.1356563