Cited by 236RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

Extensive Degradation of RNA Precursors by the Exosome in Wild-Type Cells

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Gudipati, Rajani Kanth, Xu, Zhenyu, Lebreton, Alice, Séraphin, Bertrand, Steinmetz, Lars M., Jacquier, Alain, Libri, Domenico·2012·Molecular Cell

Abstract

The exosome is a complex involved in the maturation of rRNA and sn-snoRNA, in the degradation of short-lived noncoding RNAs, and in the quality control of RNAs produced in mutants. It contains two catalytic subunits, Rrp6p and Dis3p, whose specific functions are not fully understood. We analyzed the transcriptome of combinations of Rrp6p and Dis3p catalytic mutants by high-resolution tiling arrays. We show that Dis3p and Rrp6p have both overlapping and specific roles in degrading distinct classes of substrates. We found that transcripts derived from more than half of intron-containing genes are degraded before splicing. Surprisingly, we also show that the exosome degrades large amounts of tRNA precursors despite the absence of processing defects. These results underscore the notion that large amounts of RNAs produced in wild-type cells are discarded before entering functional pathways and suggest that kinetic competition with degradation proofreads the efficiency and accuracy of processing.

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Crossref · 10.1016/j.molcel.2012.08.018

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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 [67]

    The Introduction and Results section on CUTs and SUTs identify noncoding RNAs as exosome targets, supporting the general point. Our copy does not establish the listed examples—PROMPTs, antisense transcripts, and lncRNAs—as exosome targets. The statement about differential expression across five datasets is the citing authors’ own result, not a finding attributed to this source. (LLM, conf=0.82)

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Research works printed but not linked: 2

  1. Andrulis ED Werner J Nazarian A Erdjument-Bromage H Tempst P Lis JT 2002 The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila Nature 420 837 841 12490954
  2. Huber W Toedling J Steinmetz LM 2006 Transcript mapping with high-density oligonucleotide tiling arrays Bioinformatics 22 1963 1970 16787969

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Authors
Gudipati, R. K., Xu, Z., Lebreton, A., Séraphin, B., Steinmetz, L. M., Jacquier, A., & Libri, D.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • European Molecular Biology Laboratory (DE)
Corresponding author
Libri, Domenico
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2012-11
Volume
48
Issue
3
Pages
409-421
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2000153470
Cited by
236
References
60
Citations by year
2026: 8 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 8 · 2021: 25 · 2020: 15 · 2019: 20 · 2018: 13 · 2017: 17 · 2016: 21 · 2015: 27 · 2014: 28 · 2013: 27 · 2012: 2
FWCI
10.81
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion)
Funders
  • Agence Nationale de la Recherche (ANR-08-BLAN-0038)
  • National Human Genome Research Institute (P01HG000205)
  • National Institute of General Medical Sciences (R01GM068717)
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, Rrp6p, catalytic mutant, tRNA precursors, RNA quality control, transcriptome, rRNA maturation
MeSH terms
Introns, Mutation, RNA Precursors, RNA Processing, Post-Transcriptional, RNA, Fungal, RNA, Ribosomal, RNA, Transfer, Saccharomyces cerevisiae, Substrate Specificity, Blotting, Northern, Oligonucleotide Array Sequence Analysis, RNA, Small Nucleolar, Gene Expression Profiling, Saccharomyces cerevisiae Proteins, Exosome Multienzyme Ribonuclease Complex

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