Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway
Open accessAbstract
Synthesis of ribosomal RNA (rRNA) is a key step in ribosome biogenesis and is essential for cell growth. Few studies, however, have investigated rRNA synthesis regulation in vivo in multicellular organisms. Here, we present a genetic analysis of transcription initiation factor IA (TIF-IA), a conserved RNA polymerase I transcription factor. Drosophila melanogaster Tif-IA−/− mutants have reduced levels of rRNA synthesis and sustain a developmental arrest caused by a block in cellular growth. We find that the target of rapamycin (TOR) pathway regulates TIF-IA recruitment to rDNA. Furthermore, we show that the TOR pathway regulates rRNA synthesis in vivo and that TIF-IA overexpression can maintain rRNA transcription when TOR activity is reduced in developing larvae. We propose that TIF-IA acts in vivo as a downstream growth–regulatory target of the TOR pathway. Overexpression of TIF-IA also elevates levels of both 5S RNA and messenger RNAs encoding ribosomal proteins. Stimulation of rRNA synthesis by TIF-IA may therefore provide a feed-forward mechanism to coregulate the levels of other ribosome components.
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Drosophila melanogaster lacks UBF homolog, while Tif-IA and the SL1-like complex were described in the fruit fly.
“Drosophila melanogaster lacks UBF homolog, while Tif-IA and the SL1-like complex were described in the fruit fly (68,88).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [88]
The Results and discussion state that D. melanogaster has no obvious UBF homologue, and the Introduction identifies and studies its TIF-IA homologue. Our copy does not describe an SL1-like complex in the fruit fly; the SL1 mention found is in a reference about human RNA polymerase I. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Grewal, S. S., Evans, J. R., & Edgar, B. A.
- Affiliations
- University of Calgary (CA)
- Fred Hutch Cancer Center (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-12-17
- Volume
- 179
- Issue
- 6
- Pages
- 1105-1113
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2140016
- OpenAlex
- W2042125907
- Cited by
- 95
- References
- 34
- Citations by year
- 2025: 6 · 2024: 1 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 8 · 2014: 12 · 2013: 7 · 2012: 5
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-51186, R01GM051186)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- 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
- TIF-IA, ribosomal RNA synthesis, ribosome biogenesis, TOR signaling, RNA polymerase I, rDNA transcription, cell growth regulation, developmental arrest, 5S rRNA, ribosomal protein mRNAs, Drosophila melanogaster
- MeSH terms
- Animals, DNA, Ribosomal, Drosophila melanogaster, Larva, Mutation, Protein Kinases, Ribosomes, RNA Precursors, RNA, Messenger, RNA, Ribosomal, Transcription Factors, Transcription, Genetic, Signal Transduction, Phosphatidylinositol 3-Kinases, Drosophila Proteins, Cell Enlargement, TOR Serine-Threonine Kinases
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