| First Author | Pefanis E | Year | 2015 |
| Journal | Cell | Volume | 161 |
| Issue | 4 | Pages | 774-89 |
| PubMed ID | 25957685 | Mgi Jnum | J:223317 |
| Mgi Id | MGI:5648666 | Doi | 10.1016/j.cell.2015.04.034 |
| Citation | Pefanis E, et al. (2015) RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161(4):774-89 |
| abstractText | We have ablated the cellular RNA degradation machinery in differentiated B cells and pluripotent embryonic stem cells (ESCs) by conditional mutagenesis of core (Exosc3) and nuclear RNase (Exosc10) components of RNA exosome and identified a vast number of long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) with emergent functionality. Unexpectedly, eRNA-expressing regions accumulate R-loop structures upon RNA exosome ablation, thus demonstrating the role of RNA exosome in resolving deleterious DNA/RNA hybrids arising from active enhancers. We have uncovered a distal divergent eRNA-expressing element (lncRNA-CSR) engaged in long-range DNA interactions and regulating IgH 3' regulatory region super-enhancer function. CRISPR-Cas9-mediated ablation of lncRNA-CSR transcription decreases its chromosomal looping-mediated association with the IgH 3' regulatory region super-enhancer and leads to decreased class switch recombination efficiency. We propose that the RNA exosome protects divergently transcribed lncRNA expressing enhancers by resolving deleterious transcription-coupled secondary DNA structures, while also regulating long-range super-enhancer chromosomal interactions important for cellular function. |
