Cited by 6RNA Research and SplicingNuclear Structure and FunctionGenomics and Chromatin Dynamics

Defining the roles of the Integrator, NEXT, and nuclear exosome complexes in Drosophila oogenesis

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Lee, Yongjin, Biasini, Adriano, Tipping, Cindy, Hong, Seong Hyeon, Zamore, Phillip D.·2025·Cell Reports

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Abstract

Nuclear RNA homeostasis depends on the balance of transcription, RNA processing, degradation, and transport between the nucleus and cytoplasm. RNA degradation directed by the Integrator, nuclear exosome targeting (NEXT), and nuclear exosome complexes controls the accumulation of aberrant nuclear RNA. Here, we report that Drosophila oogenesis requires the Integrator, NEXT, and nuclear exosome complexes. Depletion of Integrator, NEXT, or nuclear exosome components in Drosophila female germ cells causes infertility and accumulation of 3' extended small nuclear RNAs, promoter upstream transcripts, and cryptic transcripts. Our data highlight the essential role of nuclear RNA degradation and processing in Drosophila oogenesis and provide a catalog of RNAs whose nuclear levels are regulated by these three complexes. We propose that Integrator, NEXT, and the nuclear exosome support oogenesis by ensuring that inappropriate transcription does not overwhelm the limited supply of proteins that bind, process, and traffic RNA.

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Crossref · 10.1016/j.celrep.2025.116329

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  • The Integrator complex plays a role in premature RNA Polymerase II transcription termination of mRNAs and in processing of other small RNAs through mechanisms that require the RNA exosome.

    “The Integrator complex is known to play a role in premature RNA Polymerase II transcription termination of mRNAs in addition to processing of other small RNAs through mechanisms that require the RNA exosome85–87.”

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Authors
Lee, Y., Biasini, A., Tipping, C., Hong, S. H., & Zamore, P. D.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Zamore, Phillip D.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2025-10
Volume
44
Issue
10
Pages
116329
ISSN
2211-1247 (ISSN-L)
OpenAlex
W4414478552
Cited by
6
References
140
Citations by year
2026: 5 · 2025: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35 GM136275)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
Integrator complex, nuclear exosome, Drosophila oogenesis, female germ cells, RNA degradation, small nuclear RNA, infertility, RNA processing
MeSH terms
Animals, Cell Nucleus, Drosophila melanogaster, Female, Oogenesis, RNA Stability, Drosophila Proteins, Exosomes, Exosome Multienzyme Ribonuclease Complex

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