Retrotransposition and Crystal Structure of an Alu RNP in the Ribosome-Stalling Conformation

Mol Cell. 2015 Dec 3;60(5):715-727. doi: 10.1016/j.molcel.2015.10.003. Epub 2015 Nov 12.

Abstract

The Alu element is the most successful human genomic parasite affecting development and causing disease. It originated as a retrotransposon during early primate evolution of the gene encoding the signal recognition particle (SRP) RNA. We defined a minimal Alu RNA sufficient for effective retrotransposition and determined a high-resolution structure of its complex with the SRP9/14 proteins. The RNA adopts a compact, closed conformation that matches the envelope of the SRP Alu domain in the ribosomal translation elongation factor-binding site. Conserved structural elements in SRP RNAs support an ancient function of the closed conformation that predates SRP9/14. Structure-based mutagenesis shows that retrotransposition requires the closed conformation of the Alu ribonucleoprotein particle and is consistent with the recognition of stalled ribosomes. We propose that ribosome stalling is a common cause for the cis-preference of the mammalian L1 retrotransposon and for the efficiency of the Alu RNA in hijacking nascent L1 reverse transcriptase.

Keywords: LINE; RNA structure; SINE; mobile DNA; molecular evolution; translational control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements*
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Structure, Tertiary
  • RNA / chemistry*
  • RNA / metabolism
  • Ribosomes / metabolism*
  • Signal Recognition Particle / chemistry*
  • Signal Recognition Particle / metabolism

Substances

  • SRP14 protein, human
  • SRP9 protein, human
  • Signal Recognition Particle
  • RNA

Associated data

  • PDB/5AOX