期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 28, 页码 11574-11579出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0704946104
关键词
messenger ribonucleoprotein remodeling; nonsense-mediated mRNA; decay; pre-mRNA splicing
资金
- NIGMS NIH HHS [GM42699, R37 GM042699, R01 GM042699] Funding Source: Medline
Pre-mRNA splicing not only removes introns and joins exons to generate spliced mRNA but also results in remodeling of the spliced messenger ribonucleoprotein, influencing various downstream events. This remodeling includes the loading of an exon-exon junction complex (EX). It is unclear how the spliceosome recruits the EX onto the mRNA and whether EX formation or EJC components are required for pre-mRNA splicing. Here we immunodepleted the EX core component eIF4A3 from HeLa cell nuclear extract and found that eIF4A3 is dispensable for pre-mRNA splicing in vitro. However, eIF4A3 is required for the splicing-dependent loading of the Y14/Magoh heterodimer onto mRNA, and this activity of human eIF4A3 is also present in the Drosophila ortholog. Surprisingly, the loading of six other EX components was not affected by eIF4A3 depletion, suggesting that their binding to mRNA involves different or redundant pathways. Finally, we found that the assembly of the EX onto mRNA occurs at the late stages of the splicing reaction and requires the second-step splicing and mRNA-release factor HRH1/hPrp22. The EK-dependent and -independent recruitment of RNA-binding proteins onto rnRNA suggests a role for the EX in messenger ribonucleoprotein remodeling involving interactions with other proteins already bound to the pre-mRNA, which has implications for nonsense-mediated mRNA decay and other mRNA transactions.
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