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IRES-mediated cap-independent translation, a path leading to hidden proteome
Yun Yang 1,* and Zefeng Wang 1,2,3,*
1 CAS Key Laboratory of Computational Biology, Biomedical Big Data Center, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China
2 University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3 CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
*Correspondence to:Zefeng Wang, E-mail:; Yun Yang, E-mail:
J Mol Cell Biol, Volume 11, Issue 10, October 2019, Pages 911-919
Keyword: IRES, ITAF, translation, bicistronic system, circular RNA

Most eukaryotic mRNAs are translated in a cap-dependent fashion; however, under stress conditions, the cap-independent translation driven by internal ribosomal entry sites (IRESs) can serve as an alternative mechanism for protein production. Many IRESs have been discovered from viral or cellular mRNAs to promote ribosome assembly and initiate translation by recruiting different trans-acting factors. Although the mechanisms of translation initiation driven by viral IRESs are relatively well understood, the existence of cellular IRESs is still under debate due to the limitations of translation reporter systems used to assay IRES activities. A recent screen identified > 1000 putative IRESs from viral and human mRNAs, expanding the scope and mechanism for cap-independent translation. Additionally, a large number of circular RNAs lacking free ends were identified in eukaryotic cells, many of which are found to be translated through IRESs. These findings suggest that IRESs may play a previously unappreciated role in driving translation of the new type of mRNA, implying a hidden proteome produced from cap-independent translation.