Transcriptome-wide Analysis of Exosome Targets
Open accessAbstract
The exosome plays major roles in RNA processing and surveillance but the in vivo target range and substrate acquisition mechanisms remain unclear. Here we apply in vivo RNA crosslinking (CRAC) to the nucleases (Rrp44, Rrp6), two structural subunits (Rrp41, Csl4) and a cofactor (Trf4) of the yeast exosome. Analysis of wild-type Rrp44 and catalytic mutants showed that both the CUT and SUT classes of non-coding RNA, snoRNAs and, most prominently, pre-tRNAs and other Pol III transcripts are targeted for oligoadenylation and exosome degradation. Unspliced pre-mRNAs were also identified as targets for Rrp44 and Rrp6. CRAC performed using cleavable proteins (split-CRAC) revealed that Rrp44 endonuclease and exonuclease activities cooperate on most substrates. Mapping oligoadenylated reads suggests that the endonuclease activity may release stalled exosome substrates. Rrp6 was preferentially associated with structured targets, which frequently did not associate with the core exosome indicating that substrates follow multiple pathways to the nucleases.
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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 [66]
The Introduction identifies yeast cryptic unstable transcripts, stable unannotated transcripts, and short promoter-associated RNAs as exosome substrates; the Discussion also describes degradation of the first two classes. This supports the general point that noncoding RNAs are exosome targets, but our copy does not specifically identify PROMPTs, antisense transcripts, or lncRNAs as those targets. The observation about differential expression across five datasets appears to be the citing authors’ own finding, not a finding attributed to this source. (LLM, conf=0.84)
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References 43 · Cited by 195
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- Authors
- Schneider, C., Kudla, G., Wlotzka, W., Tuck, A., & Tollervey, D.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Schneider, Claudia
- Tollervey, David
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 48
- Issue
- 3
- Pages
- 422-433
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3526797
- OpenAlex
- W2163805932
- Cited by
- 195
- References
- 43
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 4 · 2023: 11 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 23 · 2018: 13 · 2017: 15 · 2016: 26 · 2015: 14 · 2014: 17 · 2013: 26 · 2012: 2
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Wellcome Trust (092076, 077248)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- exosomes, RNA degradation, Rrp6, TRF4, pre-tRNA, small nucleolar RNA, non-coding RNA, pre-mRNA, RNA processing, RNA surveillance, Saccharomyces cerevisiae
- MeSH terms
- Binding Sites, Mutation, Nuclear Proteins, Protein Binding, RNA Precursors, RNA Processing, Post-Transcriptional, RNA, Fungal, Saccharomyces cerevisiae, Blotting, Northern, Gene Expression Regulation, Fungal, Gene Expression Profiling, Saccharomyces cerevisiae Proteins, Exosome Multienzyme Ribonuclease Complex
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