Transcriptional Control by Premature Termination: A Forgotten Mechanism

• Published in: Trends in genetics 2019-08, Vol.35 (8), p.553-564
• Main Authors: Kamieniarz-Gdula, Kinga, Proudfoot, Nick J.
• Format: Article
• Language: English
• Subjects: alternative last exon (ALE); alternative polyadenylation (APA); Animals; Bacteria - genetics; Codon, Nonsense - genetics; Exons - genetics; Gene Expression Regulation - genetics; intronic polyadenylation (IPA); Introns - genetics; Plants - genetics; Polyadenylation - genetics; premature transcription termination; RNA, Messenger - genetics; RNA, Untranslated - genetics; transcription attenuation; Transcription Initiation Site; Transcription Termination, Genetic; Transcription, Genetic; Transcriptome; Yeasts - genetics
• ISSN: 0168-9525; 0168-9525
• DOI: 10.1016/j.tig.2019.05.005

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. PTT is widespread in metazoans. It can occur close to the TSS or further downstream in the gene body.PTT generates transcripts that, depending on the circumstances, are either rapidly degraded, or are stabilised by polyadenylation, thus contributing to transcriptome diversification.Stable premature transcripts can have independent functions as noncoding (nc)RNA or mRNA encoding proteins with different properties compared with those generated by the full-length transcript.PTT can negatively regulate expression of the full-length transcript and especially controls genes encoding transcriptional regulators.Factors triggering PTT include not only canonical RNA 3′ processing and termination factors, but also other players. Many metazoan factors oppose PTT, thus limiting its damaging potential.