Abstract

The concept of early termination as an important means of transcriptional control has long been established. Even so, its role in metazoan gene expression is underappreciated. Recent technological advances provide novel insights into premature transcription termination (PTT). This process is frequent, widespread, and can occur close to the transcription start site (TSS), or within the gene body. Stable prematurely terminated transcripts contribute to the transcriptome as instances of alternative polyadenylation (APA). Independently of transcript stability and function, premature termination opposes the formation of full-length transcripts, thereby negatively regulating gene expression, especially of transcriptional regulators. Premature termination can be beneficial or harmful, depending on its context. As a result, multiple factors have evolved to control this process.

Highlights

  • transcription start site (TSS)-Linked Premature Transcription Termination premature transcription termination (PTT) of a protein-coding gene can be divided into termination events occurring close to the TSS or within the gene body (Figure 1)

  • While this article was in review, a new study described a role for previously uncharacterised Polymerase II (Pol II) CTD-binding proteins SCAF4 and SCAF8 in binding to RNA upstream of early Polyadenylation site (PAS) and suppressing PTT in ~1300 human genes

  • Concluding Remarks and Future Perspectives Here, we have outlined recent evidence that demonstrates the widespread occurrence of PTT in protein-coding genes, both TSS proximal and intragenic

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Summary

Trends in Genetics

The concept of early termination as an important means of transcriptional control has long been established. Recent technological advances provide novel insights into premature transcription termination (PTT) This process is frequent, widespread, and can occur close to the transcription start site (TSS), or within the gene body. Many metazoan factors oppose PTT, limiting its damaging potential For many genes, their TSS is characterised by high accumulation of Pol II, as measured by chromatin immunoprecipitation (ChIP). Their TSS is characterised by high accumulation of Pol II, as measured by chromatin immunoprecipitation (ChIP) This depends on the action of negative elongation factor (NELF) and DRB sensitivity-inducing factor (DSIF), typically occurring 30–50 base pairs downstream of the TSS [17]. Premature transcription termination (PTT): early release of Pol II from the gene template between the

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