Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a

Ji Ye Yin, Zizheng Dong, Ran Yi Liu, Juan Chen, Zhao Qian Liu, Jian-Ting Zhang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

RPA2 is a subunit of a trimeric replication protein A (RPA) complex important for DNA repair and replication. Although it is known that RPA activity is regulated by post-translational modification, whether RPA expression is regulated and the mechanism therein is currently unknown. eIF3a, the largest subunit of eIF3, is an important player in translational control and has been suggested to regulate translation of a subset of messenger RNAs important for tumorigenesis, metastasis, cell cycle progression, drug response and DNA repair. In the present study, we show that RPA2 expression is regulated at translational level via internal ribosome entry site (IRES)-mediated initiation in response to DNA damage. We also found that eIF3a suppresses RPA2 synthesis and inhibits its cellular IRES activity by directly binding to the IRES element of RPA2 located at -50 to -150 bases upstream of the translation start site. Taken together, we conclude that RPA2 expression is translationally regulated via IRES and by eIF3a and that this regulation is partly accountable for cellular response to DNA damage and survival.

Original languageEnglish
Pages (from-to)1224-1231
Number of pages8
JournalCarcinogenesis
Volume34
Issue number6
DOIs
StatePublished - Jun 2013

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Replication Protein A
DNA Repair
DNA Damage
Post Translational Protein Processing
DNA Replication
Cell Cycle
Carcinogenesis
Neoplasm Metastasis
Messenger RNA
Internal Ribosome Entry Sites
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research

Cite this

Yin, J. Y., Dong, Z., Liu, R. Y., Chen, J., Liu, Z. Q., & Zhang, J-T. (2013). Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a. Carcinogenesis, 34(6), 1224-1231. https://doi.org/10.1093/carcin/bgt052

Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a. / Yin, Ji Ye; Dong, Zizheng; Liu, Ran Yi; Chen, Juan; Liu, Zhao Qian; Zhang, Jian-Ting.

In: Carcinogenesis, Vol. 34, No. 6, 06.2013, p. 1224-1231.

Research output: Contribution to journalArticle

Yin, JY, Dong, Z, Liu, RY, Chen, J, Liu, ZQ & Zhang, J-T 2013, 'Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a', Carcinogenesis, vol. 34, no. 6, pp. 1224-1231. https://doi.org/10.1093/carcin/bgt052
Yin, Ji Ye ; Dong, Zizheng ; Liu, Ran Yi ; Chen, Juan ; Liu, Zhao Qian ; Zhang, Jian-Ting. / Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a. In: Carcinogenesis. 2013 ; Vol. 34, No. 6. pp. 1224-1231.
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