Cited by 119RNA Research and SplicingGenomics and Chromatin DynamicsRNA and protein synthesis mechanisms

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation

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Abstract

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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  1. Kiledjian, M., Burd, C. G., Görlach, M., Portman, D. S. & Dreyfuss, G. in Frontiers in Molecular Biology (eds Mattaj, I. & Nagai, K. ) 127–149 (Oxford Univ. Press, 1994)

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Metadata

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.
Venue
Nature
Published
2012-03-25
Volume
484
Issue
7394
Pages
386-389
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
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
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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