Degradation of Non-coding RNAs Promotes Recycling of Termination Factors at Sites of Transcription
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Abstract
A large share of the non-coding transcriptome in yeast is controlled by the Nrd1-Nab3-Sen1 (NNS) complex, which promotes transcription termination of non-coding RNA (ncRNA) genes, and by the nuclear exosome, which limits the steady-state levels of the transcripts produced. How unconstrained ncRNA levels affect RNA metabolism and gene expression are long-standing and important questions. Here, we show that degradation of ncRNAs by the exosome is required for freeing Nrd1 and Nab3 from the released transcript after termination. In exosome mutants, these factors are sequestered by ncRNAs and cannot be efficiently recycled to sites of transcription, inducing termination defects at NNS targets. ncRNA-dependent, genome-wide termination defects can be recapitulated by the expression of a degradation-resistant, circular RNA containing a natural NNS target in exosome-proficient cells. Our results have important implications for the mechanism of termination, the general impact of ncRNAs abundance, and the importance of nuclear ncRNA degradation.
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Many transcripts differentially expressed in all five datasets were noncoding RNAs, which are well established targets for the RNA exosome and can include PROMPTs, antisense transcripts, and long noncoding RNAs.
“Many of the transcripts that were differentially expressed in all five datasets were noncoding RNAs, which are well established to be targets for the RNA exosome and can include PROMPTs, antisense (AS) transcripts, and long noncoding RNAs (lncRNAs) as shown in Fig. 2B61–67.”
From EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery (2026) · cites this paper as [62]
The Introduction (p. 1) identifies noncoding RNAs, including cryptic unstable transcripts, as targets of exosome-mediated degradation and describes antisense noncoding transcription. It does not establish PROMPTs or long noncoding RNAs as examples of those targets. The five-dataset observation is the citing paper’s own result, not a finding attributed to this source. (LLM, conf=0.84)
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Ogami, K., Zheng, M., Yoshino, S., Sugimoto, Y., Seida, M., Mori, T., Yoshizawa, R., Onimaru, K., Kadota, M., Kuraku, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.06.658161 · Cited by 3 · see citing works
Tho2 is critical for the recruitment of Rrp6 to chromatin in response to perturbed mRNP biogenesis
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EXOSC3 G191 Variants Trigger System-Wide Recalibration of RNA Processing Machinery
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A transcription termination mechanism for maintaining homogeneous protein expression
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Mechanisms of transcription termination across the coding and noncoding loci of the genome
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- Authors
- Villa, T., Barucco, M., Martin-Niclos, M.-J., Jacquier, A., & Libri, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Villa, Tommaso
- Libri, Domenico
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 32
- Issue
- 3
- Pages
- 107942
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3044180160
- Cited by
- 37
- References
- 67
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 1
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- Funders
- Fondation pour la Recherche Médicale
- Labex (ANR-11-LABX-0071)
- Centre National de la Recherche Scientifique
- Université de Paris (ANR-18-IDEX-0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- nuclear exosome, transcription termination, circular RNA, Saccharomyces cerevisiae, RNA metabolism
- MeSH terms
- Cell Nucleus, Models, Genetic, RNA, Fungal, Saccharomyces cerevisiae, Transcription Factors, Gene Expression Regulation, Fungal, Genome, Fungal, RNA Stability, RNA, Untranslated, Saccharomyces cerevisiae Proteins, Exosomes, Transcriptome, Transcription Termination, Genetic
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