R-Loops as Cellular Regulators and Genomic Threats.

During transcription, the nascent RNA strand can base pair with its template DNA, displacing the non-template strand as ssDNA and forming a structure called an R-loop. R-loops are common across many domains of life and cause DNA damage in certain contexts. In this review, we summarize recent results implicating R-loops as important regulators of cellular processes such as transcription termination, gene regulation, and DNA repair.

Targeting Functional Noncoding RNAs.

Noncoding RNAs have essential biochemical functions in different areas of cellular metabolism, including protein synthesis, RNA splicing, protein secretion, and DNA replication. We have successfully used Morpholino antisense oligonucleotides for the functional inactivation of small noncoding RNAs required for DNA replication (Y RNAs in vertebrates and stem-bulge RNAs in nematodes). Here we discuss specific issues of targeting functional noncoding RNAs for inactivation by Morpholino antisense oligonucleotides.

Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage.

The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage.