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Mammalian cells repress random DNA that yeast transcribes

In experiments dubbed the Random Genome Project, researchers have integrated DNA strands with random sequences into yeast and mouse cells to find the default transcriptional state of their genomes.
  1. Sean R. Eddy

    1. Sean R. Eddy is in the Department of Molecular and Cellular Biology and the Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.

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More of the DNA in the human genome is transcribed into RNAs than scientists can adequately account for. Transcription of around 20,000 known protein-coding genes covers about 40% of the genome, but at least 75% of the genome is transcribed reproducibly at a detectable level1,2. A decades-old debate in genomics has failed to resolve how much of the extra RNA transcribed — including thousands of long non-coding RNA sequences — is functional, and how much is ‘noise’3,4. Central to the disagreement is a lack of clarity about the nature of this transcriptional noise5. In 2013, I suggested a ‘Random Genome Project’ to establish a baseline expectation for the biochemical activity of genomic DNA in the absence of any evolutionary selection for biological functions6. Fuelled by rapid advances in synthetic genomics, two studies, one in Nature7 and one in Nature Structural and Molecular Biology8, describe versions of this experiment in yeast (Saccharomyces cerevisiae) and in mammalian cells.

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Nature 628, 271-273 (2024)

doi: https://doi.org/10.1038/d41586-024-00575-x

References

  1. ENCODE Project Consortium. Nature 489, 57–74 (2012).

    Article  PubMed  Google Scholar 

  2. Djebali, S. et al. Nature 489, 101–108 (2012).

    Article  PubMed  Google Scholar 

  3. Palazzo, A. F. & Lee, E. S. Front. Genet. 6, 2 (2015).

    Article  PubMed  Google Scholar 

  4. Ponting, C. P. & Haerty, W. Annu. Rev. Genom. Hum. Genet. 23, 153–172 (2022).

    Article  Google Scholar 

  5. Struhl, K. Nature Struct. Mol. Biol. 14, 103–105 (2007).

    Article  PubMed  Google Scholar 

  6. Eddy, S. R. Curr. Biol. 23, R259–R261 (2013).

    Article  PubMed  Google Scholar 

  7. Camellato, B. R. et al. Nature 628, 373–380 (2024).

    Article  Google Scholar 

  8. Luthra, I. et al. Nature Struct. Mol. Biol. https://doi.org/10.1038/s41594-024-01235-4 (2024).

    Article  Google Scholar 

  9. Gvozdenov, Z., Barcutean, Z. & Struhl, K. Mol. Cell 83, 1786–1797 (2023).

    Article  PubMed  Google Scholar 

  10. Zhou, J. et al. Sci. China Life Sci. 65, 851–860 (2022).

    Article  PubMed  Google Scholar 

  11. Chapard, C. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.12.21.520625 (2023).

  12. Seczynska, M. & Lehner, P. J. Trends Genet. 39, 251–267 (2023).

    Article  PubMed  Google Scholar 

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Competing Interests

The author declares no competing interests.

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