Structure of the RNA Specialized Translation Initiation Element that Recruits eIF3 to the 5′-UTR of c-Jun. Issue 7 (27th March 2020)

• Record Type: Journal Article
• Authors: Walker, Matthew J.; Shortridge, Matthew D.; Albin, Dreycey D.; Cominsky, Lauren Y.; Varani, Gabriele
• Is Part Of: Journal of molecular biology. Volume 432:Issue 7(2020)
• Page Start: 1841
• Page End: 1855
• Publication Date: 2020-03-27
• Subjects: RNA structure -- NMR -- eIF3 recognition -- specialized translation initiation -- IRES; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.01.001
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Specialized translation initiation is a novel form of regulation of protein synthesis, whereby RNA structures within the 5′-UTR regulate translation rates of specific mRNAs. Similar to internal ribosome entry sites (IRESs), specialized translation initiation requires the recruitment of eukaryotic initiation factor 3 (eIF3), but also requires cap recognition by eIF3d, a new 5′-m 7 GTP recognizing protein. How these RNA structures mediate eIF3 recruitment to affect translation of specific mRNAs remains unclear. Here, we report the nuclear magnetic resonance (NMR) structure of a stem-loop within the c-JUN 5′ UTR recognized by eIF3 and essential for specialized translation initiation of this well-known oncogene. The structure exhibits similarity to eIF3 recognizing motifs found in hepatitis C virus (HCV)–like IRESs, suggesting mechanistic similarities. This work establishes the RNA structural features involved in c-JUN specialized translation initiation and provides a basis to search for small molecule inhibitors of aberrant expression of the proto-oncogenic c-JUN. Graphical abstract: Image 1 Highlights: The NMR structure of the c-JUN specialized translation initiation RNA element is reported. The structure is modeled into the known HCV IRES eIF3 recognition site. Both c-JUN elements and HCV-like IRES IIIb subdomains exhibit enlarged major grooves. A unified view of eIF3 recruitment to IRES and specialized translation initiation elements is proposed.