Nature structural & molecular biologyOct 29, 2026

How the R2 Retrotransposon Works with CRISPR-Cas9 to Insert Genes in Specific Places

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Nov 2, 2026

Abstract

Cryo-electron microscopy reveals the structure of the R2Tg-template RNA-target DNA complex in the TPRT initiation state.

R2 retroelements insert into 28S ribosomal DNA loci in diverse eukaryotes through a process called target-primed reverse transcription.
The avian R2 system from Taeniopygia guttata can introduce a sequence payload into human cells.
Structural insights into the R2Tg-mediated process provide a better understanding of its function and context.
A combined approach using structural data and computational protein design methods may enhance the STITCHR system for gene integration.

Simplified

R2 retroelements are non-long-terminal-repeat retrotransposons that primarily insert into 28S ribosomal DNA loci across diverse eukaryotes. R2 elements home to their target sites through target-primed reverse transcription (TPRT), in which the R2 protein recognizes and nicks the target DNA to prime reverse transcription using an R2-encoding RNA as the template. The avian R2 system from Taeniopygia guttata (R2Tg) can insert a payload sequence within an RNA template into 28S ribosomal DNA loci in human cells. Here, we present cryo-electron microscopy structures of the R2Tg-template RNA-target DNA complex in the TPRT initiation state, both alone and bound to a Cas9-guide RNA complex. These structures provide mechanistic insights into R2Tg-mediated TPRT in its natural context and in the programmable gene integration system STITCHR (site-specific target-primed insertion through targeted CRISPR homing of retroelements). Furthermore, we combine these structural insights with computational protein design methods to engineer an enhanced STITCHR system.

Full Text

Full text is available at the source.

View Full Text ↗

How the R2 Retrotransposon Works with CRISPR-Cas9 to Insert Genes in Specific Places

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief