Complex determinants of R-loop formation at transposable elements and major DNA satellites

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Aberrant transposable element (TE) activation is a known cause of genomic instability and disease.
• The role of DNA:RNA hybrids (R-loops) in TE-mediated genomic disruption is largely unexplored.

Purpose of the Study:

• To investigate R-loop formation at transposable elements (TEs) and satellite DNA in Drosophila melanogaster ovaries.
• To determine the factors influencing R-loop formation at repetitive elements and their potential impact on host genomes.

Main Methods:

• Utilized DNA:RNA immunoprecipitation followed by high-throughput sequencing (DRIP-seq) to map R-loop profiles.
• Analyzed R-loop formation in control and rhino knockout Drosophila melanogaster ovaries.
• Examined the correlation between R-loop formation, sequence content, expression levels, and population frequencies of TEs and satellites.

Main Results:

• R-loops predominantly form in LTR retrotransposons with A/T-rich motifs and at several abundant DNA satellites.
• R-loop formation correlates positively with expression levels for both TEs and satellites.
• Evidence suggests TE copies with high R-loop signals may be under negative selection, indicating potential harm to the host.

Conclusions:

• R-loop formation occurs at specific repetitive elements in Drosophila, influenced by sequence and expression, but other factors are also involved.
• TE-associated R-loops might represent a mechanism of genomic instability, potentially being selected against by the host.