A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs

被引:125
作者
Lee, Amy Si-Ying [1 ]
Burdeinick-Kerr, Rebeca [1 ]
Whelan, Sean P. J. [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
ribosome code; rhabdovirus; alternative translation; uba52; paramyxovirus; PROTEIN-SYNTHESIS; ENTRY SITE; IN-VITRO; SACCHAROMYCES-CEREVISIAE; INTERNAL INITIATION; C-MYC; CELLS; SUBUNIT; BINDING; IRES;
D O I
10.1073/pnas.1216454109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Initiation is the primary target of translational control for all organisms. Regulation of eukaryotic translation is traditionally thought to occur through initiation factors and RNA structures. Here, we characterize a transcript-specific translation initiation mechanism that is mediated by the ribosome. By studying vesicular stomatitis virus (VSV), we identify the large ribosomal subunit protein rpL40 as requisite for VSV cap-dependent translation but not bulk cellular or internal ribosome entry site-driven translation. This requirement is conserved among members of the order Mononegavirales, including measles virus and rabies virus. Polysome analyses and in vitro reconstitution of initiation demonstrate that rpL40 is required for 80S formation on VSV mRNAs through a cis-regulatory element. Using deep sequencing, we further uncover a subset of cellular transcripts that are selectively sensitive to rpL40 depletion, suggesting VSV may have usurped an endogenous translation pathway. Together, these findings demonstrate that the ribosome acts as a translational regulator outside of its catalytic role during protein synthesis.
引用
收藏
页码:324 / 329
页数:6
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