The Lsm1-7-Pat1 complex promotes viral RNA translation and replication by differential mechanisms
- Jennifer Jungfleisch1,3,
- Ashis Chowdhury2,3,
- Isabel Alves-Rodrigues1,3,
- Sundaresan Tharun2 and
- Juana Díez1
- 1Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- 2Department of Biochemistry, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland 20814-4799, USA
- Corresponding authors: juana.diez{at}upf.edu, tharun.sundaresan{at}usuhs.edu
-
↵3 These authors contributed equally to this work.
Abstract
The Lsm1-7-Pat1 complex binds to the 3′ end of cellular mRNAs and promotes 3′ end protection and 5′–3′ decay. Interestingly, this complex also specifically binds to cis-acting regulatory sequences of viral positive-strand RNA genomes promoting their translation and subsequent recruitment from translation to replication. Yet, how the Lsm1-7-Pat1 complex regulates these two processes remains elusive. Here, we show that Lsm1-7-Pat1 complex acts differentially in these processes. By using a collection of well-characterized lsm1 mutant alleles and a system that allows the replication of Brome mosaic virus (BMV) in yeast we show that the Lsm1-7-Pat1 complex integrity is essential for both, translation and recruitment. However, the intrinsic RNA-binding ability of the complex is only required for translation. Consistent with an RNA-binding-independent function of the Lsm1-7-Pat1 complex on BMV RNA recruitment, we show that the BMV 1a protein, the sole viral protein required for recruitment, interacts with this complex in an RNA-independent manner. Together, these results support a model wherein Lsm1-7-Pat1 complex binds consecutively to BMV RNA regulatory sequences and the 1a protein to promote viral RNA translation and later recruitment out of the host translation machinery to the viral replication complexes.
Keywords
- Lsm1-7
- Pat1
- Lsm1-7-Pat1 complex
- decapping activators
- viral RNA
- BMV
- RNA virus
- Lsm proteins
- translation
- replication
Footnotes
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.052209.115.
- Received April 16, 2015.
- Accepted May 11, 2015.
This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
