| First Author | Austenaa LMI | Year | 2021 |
| Journal | Nat Struct Mol Biol | Volume | 28 |
| Issue | 4 | Pages | 337-346 |
| PubMed ID | 33767452 | Mgi Jnum | J:319942 |
| Mgi Id | MGI:6867107 | Doi | 10.1038/s41594-021-00572-y |
| Citation | Austenaa LMI, et al. (2021) A first exon termination checkpoint preferentially suppresses extragenic transcription. Nat Struct Mol Biol 28(4):337-346 |
| abstractText | Interactions between the splicing machinery and RNA polymerase II increase protein-coding gene transcription. Similarly, exons and splicing signals of enhancer-generated long noncoding RNAs (elncRNAs) augment enhancer activity. However, elncRNAs are inefficiently spliced, suggesting that, compared with protein-coding genes, they contain qualitatively different exons with a limited ability to drive splicing. We show here that the inefficiently spliced first exons of elncRNAs as well as promoter-antisense long noncoding RNAs (pa-lncRNAs) in human and mouse cells trigger a transcription termination checkpoint that requires WDR82, an RNA polymerase II-binding protein, and its RNA-binding partner of previously unknown function, ZC3H4. We propose that the first exons of elncRNAs and pa-lncRNAs are an intrinsic component of a regulatory mechanism that, on the one hand, maximizes the activity of these cis-regulatory elements by recruiting the splicing machinery and, on the other, contains elements that suppress pervasive extragenic transcription. |
