A first exon termination checkpoint preferentially suppresses extragenic transcription.
Liv M I AustenaaViviana PiccoloMarta RussoElena ProsperiniSara PollettiDanilo PolizzeseSerena GhislettiIros BarozziGiuseppe Riccardo DiaferiaGioacchino NatoliPublished in: Nature structural & molecular biology (2021)
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.
Keyphrases
- transcription factor
- genome wide identification
- binding protein
- dna binding
- dna damage
- cell cycle
- induced apoptosis
- genome wide
- endothelial cells
- signaling pathway
- dna methylation
- protein protein
- gene expression
- small molecule
- nucleic acid
- human immunodeficiency virus
- hiv infected
- hepatitis c virus
- pluripotent stem cells