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

• Published in: Molecular cell Vol. 60; no. 5; pp. 715 - 727
• Main Authors: Ahl, Valentina, Keller, Heiko, Schmidt, Steffen, Weichenrieder, Oliver
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-12-2015
• Subjects: Alu Elements; Animals; Binding Sites; Crystallography, X-Ray; HeLa Cells; Humans; LINE; mobile DNA; Models, Molecular; molecular evolution; Nucleic Acid Conformation; Protein Structure, Tertiary; Ribosomes - metabolism; RNA - chemistry; RNA - metabolism; RNA structure; Signal Recognition Particle - chemistry; Signal Recognition Particle - metabolism; SINE; translational control; SINE; translational control; mobile DNA; molecular evolution; RNA structure; LINE
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2015.10.003

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.
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•Identification of a minimal Alu RNA sufficient for retrotransposition•High-resolution crystal structure of a human Alu RNP in the closed conformation•An ancient Alu RNA structural core in SRP RNAs interfaces the ribosome•Targeting stalled ribosomes could overcome L1 cis-preference
Ahl et al. determined the crystal structure of a conformationally closed Alu ribonucleoprotein particle that matters for the signal recognition particle and the retrotransposition of the human Alu element. A single Alu folding unit is sufficient for retrotransposition activity. It likely targets stalling ribosomes to recruit nascent L1 reverse transcriptase.