Fail-safe transcriptional termination for protein-coding genes in S. cerevisiae
Ana G Rondón1, Hannah E Mischo, Junya Kawauchi
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Abstract:
Transcription termination of RNA polymerase II (Pol II) on protein-coding genes in S. cerevisiae relies on pA site recognition by 3' end processing factors. Here we demonstrate the existence of two alternative termination mechanisms that rescue polymerases failing to disengage from the template at pA sites. One of these fail-safe mechanisms is mediated by the NRD complex, similar to termination of short noncoding genes. The other termination mechanism is mediated by Rnt1 cleavage of the nascent transcript. Both fail-safe termination mechanisms trigger degradation of readthrough transcripts by the exosome. However, Rnt1-mediated termination can also enhance the usage of weak pA signals and thereby generate functional mRNA. We propose that these alternative Pol II termination pathways serve the dual function of avoiding transcription interference and promoting rapid removal of aberrant transcripts.
Insights
Scientists discovered two new ways RNA polymerase II (Pol II) stops transcribing genes in yeast. These backup mechanisms prevent transcription problems and clear faulty RNA molecules.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Gene Regulation
Background:
- Transcription termination in yeast relies on polyadenylation (pA) site recognition by 3' end processing factors.
- RNA polymerase II (Pol II) must disengage from DNA after transcription to prevent errors.
Purpose of the Study:
- To investigate alternative transcription termination mechanisms for protein-coding genes in Saccharomyces cerevisiae.
- To understand how polymerases failing to terminate at pA sites are handled.
Main Methods:
- Investigated the roles of the NRD complex and Rnt1 cleavage in transcription termination.
- Analyzed the impact of these mechanisms on readthrough transcripts and mRNA processing.
Main Results:
- Identified two alternative Pol II termination pathways: one involving the NRD complex and another mediated by Rnt1 cleavage.
- Both pathways trigger exosome-mediated degradation of readthrough transcripts.
- Rnt1-mediated termination can also improve the use of weak pA signals, generating functional mRNA.
Conclusions:
- Alternative Pol II termination pathways provide fail-safe mechanisms against transcription interference.
- These pathways ensure rapid removal of aberrant transcripts.
- Rnt1-mediated termination contributes to both transcript quality control and functional mRNA generation.
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