| First Author | Lai F | Year | 2020 |
| Journal | Mol Cell | Volume | 77 |
| Issue | 5 | Pages | 1032-1043.e4 |
| PubMed ID | 31924447 | Mgi Jnum | J:286183 |
| Mgi Id | MGI:6400620 | Doi | 10.1016/j.molcel.2019.12.029 |
| Citation | Lai F, et al. (2020) Directed RNase H Cleavage of Nascent Transcripts Causes Transcription Termination. Mol Cell 77(5):1032-1043.e4 |
| abstractText | An attractive approach to reduce gene expression is via the use of antisense oligonucleotides (ASOs) that harness the RNase H1 mechanism. Here we show that RNase H ASOs targeted to introns or exons robustly reduce the level of spliced RNA associated with chromatin. Surprisingly, intron-targeted ASOs reduce the level of pre-mRNA associated with chromatin to a greater extent than exon-targeted ASOs. This indicates that exon-targeted ASOs achieve full activity after the pre-mRNA has undergone splicing, but before the mRNA is released from chromatin. Even though RNase H ASOs can reduce the level of RNA associated with chromatin, the effect of ASO-directed RNA degradation on transcription has never been documented. Here we show that intron-targeted ASOs and, to a lesser extent, exon-targeted ASOs cause RNA polymerase II (Pol II) transcription termination in cultured cells and mice. Furthermore, ASO-directed transcription termination is mediated by the nuclear exonuclease XRN2. |
