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The eukaryotic translation initiation factor eIF4E elevates steady-state m7G capping of coding and noncoding transcripts
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DOI：10.1073/pnas.2002360117.png)
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Methyl-7-guanosine (m(7)G) capping of coding and some noncoding RNAs is critical for their maturation and subsequent activity. Here, we discovered that eukaryotic translation initiation factor 4E (eIF4E), itself a cap-binding protein, drives the expression of the capping machinery and increased capping efficiency of similar to 100 coding and noncoding RNAs. To quantify this, we developed enzymatic (cap quantification; CapQ) and quantitative cap immunoprecipitation (CapIP) methods. The CapQ method has the further advantage that it captures information about capping status independent of the type of 5' cap, i.e., it is not restricted to informing on m(7)G caps. These methodological advances led to unanticipated revelations: 1) Many RNA populations are inefficiently capped at steady state (similar to 30 to 50%), and eIF4E overexpression increased this to similar to 60 to 100%, depending on the RNA; 2) eIF4E physically associates with noncoding RNAs in the nucleus; and 3) approximately half of eIF4E-capping targets identified are noncoding RNAs. eIF4E's association with noncoding RNAs strongly positions it to act beyond translation. Coding and noncoding capping targets have activities that influence survival, cell morphology, and cell-to-cell interaction. Given that RNA export and translation machineries typically utilize capped RNA substrates, capping regulation provides means to titrate the protein-coding capacity of the transcriptome and, for noncoding RNAs, to regulate their activities. We also discovered a cap sensitivity element (CapSE) which conferred eIF4E-dependent capping sensitivity. Finally, we observed elevated capping for specific RNAs in high-eIF4E leukemia specimens, supporting a role for cap dysregulation in malignancy. In all, levels of capping RNAs can be regulated by eIF4E.
Keyword:
eIF4E
RNMT
methyl-7-guanosine cap
RNA capping
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9.1
论文数:
10.8W
被引数:
73.5W
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RNA guanine-7 methyltransferase catalyzes the methylation of cytoplasmically recapped RNAs.png)
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