DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
Open accessAbstract
Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript. However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles. This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex--named DBIRD--that binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in (A + T)-rich DNA, and is present at the affected exons. RNA-interference-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing.
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Depletion of DBIRD induces an accumulation of RNA Pol II on A/T-rich alternatively spliced internal exons in human cells, suggesting a role for DBIRD in the control of RNA Pol II speed over exons.
“Depletion of DBIRD, a protein complex formed by DBC1 and ZNF326, induces an accumulation of RNA Pol II on A/T‐rich alternatively spliced internal exons in human cells, suggesting a role for DBIRD in the control of RNA Pol II speed over exons (Close et al, 2012).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Close et al, 2012
The paper’s Abstract (page not specified) identifies DBIRD as a DBC1–ZIRD complex, with ZIRD identified as ZNF326. It reports that depletion changes RNAPII density in regions encompassing A/T-rich, alternatively spliced exons and supports decreased elongation rates there. The passages do not specify that RNAPII density increased, so the claimed accumulation is not established by our copy. (LLM, conf=0.83)
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- Authors
- Close, P., East, P., Dirac-Svejstrup, A. B., Hartmann, H., Heron, M., Maslen, S., Chariot, A., Söding, J., Skehel, M., & Svejstrup, J. Q.
- Affiliations
- Cancer Research UK (GB)
- Center for Integrated Protein Science Munich (DE)
- University of Liège (BE)
- Corresponding author
- Svejstrup, Jesper Q.
- ORCID
- Venue
- Nature
- Published
- 2012-03-25
- Volume
- 484
- Issue
- 7394
- Pages
- 386-389
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3378035
- OpenAlex
- W2081489843
- Cited by
- 119
- References
- 24
- Citations by year
- 2025: 6 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 8 · 2014: 14 · 2013: 20 · 2012: 8
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- ORBi (University of Liège) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Molecular Biology Organization
- Cancer Research UK (A3560, 11567)
- Fonds Léon Fredericq
- 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 › RNA and protein synthesis mechanisms
- Keywords
- DBC1, RNA polymerase II, transcription elongation, alternative splicing, messenger ribonucleoprotein, AT-rich DNA, pre-mRNA processing
- MeSH terms
- Animals, Carrier Proteins, Chromatin, Exons, Humans, Ribonucleoproteins, RNA Polymerase II, RNA, Messenger, Transcription, Genetic, Alternative Splicing, Heterogeneous-Nuclear Ribonucleoproteins, RNA Interference, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Mice, HEK293 Cells
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