The Lsm1-7-Pat1 complex promotes viral RNA translation and replication by differential mechanisms

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jun 19, 2015
Source ID
10.1261/rna.052209.115

Entities

People

  • Ashis Chowdhury
  • Isabel Alves-rodrigues
  • Jennifer Jungfleisch
  • Juana Díez
  • Sundaresan Tharun

Organizations

  • Generalitat of Catalonia
  • Ministry of Science of Spain
  • Uniformed Services University of the Health Sciences

Tags

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics