박주리 (고려대학교)

한빛사논문

조회273

고려대학교

CV File 185 kb

Nucleic Acids Res., Oct 09 2023, gkad763 | https://doi.org/10.1093/nar/gkad763 An interaction between eIF4A3 and eIF3g drives the internal initiation of translation.

Jeeyoon Chang^1,†, Min-Kyung Shin^2,†, Joori Park^2,†, Hyun Jung Hwang¹, Nicolas Locker³, Junhak Ahn⁴, Doyeon Kim⁴, Daehyun Baek⁴, Yeonkyoung Park¹, Yujin Lee², Sung Ho Boo², Hyeong-In Kim¹ and Yoon Ki Kim^1,*

¹Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea

²Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea

³Department of Microbial and Cellular Sciences, University of Surrey, Guildford GU2 7HX, UK

⁴School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea

^*To whom correspondence should be addressed. : Yoon Ki Kim

^†These authors contributed equally to this work.

Abstract

An RNA structure or modified RNA sequences can provide a platform for ribosome loading and internal translation initiation. The functional significance of internal translation has recently been highlighted by the discovery that a subset of circular RNAs (circRNAs) is internally translated. However, the molecular mechanisms underlying the internal initiation of translation in circRNAs remain unclear. Here, we identify eIF3g (a subunit of eIF3 complex) as a binding partner of eIF4A3, a core component of the exon-junction complex (EJC) that is deposited onto spliced mRNAs and plays multiple roles in the regulation of gene expression. The direct interaction between eIF4A3-eIF3g serves as a molecular linker between the eIF4A3 and eIF3 complex, thereby facilitating internal ribosomal entry. Protein synthesis from in vitro-synthesized circRNA demonstrates eIF4A3-driven internal translation, which relies on the eIF4A3-eIF3g interaction. Furthermore, our transcriptome-wide analysis shows that efficient polysomal association of endogenous circRNAs requires eIF4A3. Notably, a subset of endogenous circRNAs can express a full-length intact protein, such as β-catenin, in an eIF4A3-dependent manner. Collectively, our results expand the understanding of the protein-coding potential of the human transcriptome, including circRNAs.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-10)
연구진국내(교신)+국외 연구진
분야 생명과학 > 분자생물학

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