Mechanism of mammalian transcriptional repression by noncoding RNA
Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. 2025. Mechanism of mammalian transcriptional repression by noncoding RNA. Nature Structural & Molecular Biology.
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Abstract
Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryogenic-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation. Further, we show how distinct domains of the general transcription factor TFIIF control repressive activity. Together, we reveal how a noncoding RNA can regulate mammalian gene expression.
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2025-01-06
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Nature Structural & Molecular Biology
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Springer Nature
Acknowledgement
We thank the members of the Bernecky laboratory for helpful discussions and A. Hlavata for providing Pol II for use in the fluorescence anisotropy binding assay. We thank V.-V. Hodirnau for SerialEM data collection and support with EPU data collection. We thank D. Slade (Max Perutz Laboratories and Medical University of Vienna, Vienna, Austria) for the wild-type TFIIF expression plasmid. We thank N. Thompson and R. Burgess (McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA) for the 8WG16 hybridoma cell line. We thank C. Plaschka and M. Loose for critical reading of the manuscript. This work was supported by Austrian Science Fund (FWF) grant no. P34185 (DOI 10.55776/P34185) (C.B.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This research was further supported by the Scientific Service Units of ISTA through resources provided by the Laboratory Support Facility, Electron Microscopy Facility, Scientific Computing and the Preclinical Facility.
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Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional repression by noncoding RNA. Nature Structural & Molecular Biology. 2025. doi:10.1038/s41594-024-01448-7
Tluckova, K., Kaczmarek, B. M., Testa Salmazo, A. P., & Bernecky, C. (2025). Mechanism of mammalian transcriptional repression by noncoding RNA. Nature Structural & Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-024-01448-7
Tluckova, Katarina, Beata M Kaczmarek, Anita P Testa Salmazo, and Carrie Bernecky. “Mechanism of Mammalian Transcriptional Repression by Noncoding RNA.” Nature Structural & Molecular Biology. Springer Nature, 2025. https://doi.org/10.1038/s41594-024-01448-7.
K. Tluckova, B. M. Kaczmarek, A. P. Testa Salmazo, and C. Bernecky, “Mechanism of mammalian transcriptional repression by noncoding RNA,” Nature Structural & Molecular Biology. Springer Nature, 2025.
Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. 2025. Mechanism of mammalian transcriptional repression by noncoding RNA. Nature Structural & Molecular Biology.
Tluckova, Katarina, et al. “Mechanism of Mammalian Transcriptional Repression by Noncoding RNA.” Nature Structural & Molecular Biology, Springer Nature, 2025, doi:10.1038/s41594-024-01448-7.
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