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RNA helicase A is necessary for translation of selected messenger RNAs

Abstract

RNA helicase A (RHA) is a highly conserved DEAD-box protein that activates transcription, modulates RNA splicing and binds the nuclear pore complex. The life cycle of typical mRNA involves RNA processing and translation after ribosome scanning of a relatively unstructured 5′ untranslated region (UTR). The precursor RNAs of retroviruses and selected cellular genes harbor a complex 5′ UTR and use a yet-to-be-identified host post-transcriptional effector to stimulate efficient translation. Here we show that RHA recognizes a structured 5′-terminal post-transcriptional control element (PCE) of a retrovirus and the JUND growth-control gene. RHA interacts with PCE RNA in the nucleus and cytoplasm, facilitates polyribosome association and is necessary for its efficient translation. Our results reveal a previously unidentified role for RHA in translation and implicate RHA as an integrative effector in the continuum of gene expression from transcription to translation.

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GenBank/EMBL/DDBJ

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  • 14 May 2006

    X-axis labeled incorrectly

Notes

  1. 1.

    * NOTE: In the version of this article initially published online, the label for the x-axis in Figure 5c was incorrect. This error was introduced during the production process for the article. The correct label should read "Time 3H metabolic labeling (min).” The error has been corrected for all versions of the article. We apologize for any inconvenience this may have caused.

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Acknowledgements

We are grateful to K. Green-Church and the Ohio State University CCIC proteomics core for mass spectrophotometry, W.C. Merrick for valuable discussion, K. Hayes, I. Younis and members of the K.B.-L. laboratory for comments on the manuscript and T. Vojt for figure preparation. This work was supported by grants from the US National Institutes of Health (P01CA16058 and P30CA100730).

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Competing interests

The authors declare no competing financial interests.

Correspondence to Kathleen Boris-Lawrie.

Supplementary information

  1. Supplementary Table 1

    Oligonucleotide primers (PDF 46 kb)

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Figure 1: RNA helicase A is a PCE-binding protein.
Figure 2: Selected RNAs coimmunoprecipitate with RHA.
Figure 3: RHA downregulation eliminates PCE activity.
Figure 4: Overexpression of RHA increases PCE activity.
Figure 5: RHA is necessary for efficient translation of PCE-gag RNA.
Figure 6: RHA is necessary for efficient translation of JUND RNA.
Figure 7: RHA immunoprecipitates with JUND and PCE-gag mRNA in the nucleus and cytoplasm.
Figure 8: Model for RHA stimulating translation of PCE RNA.