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ZCCHC8 is required for the degradation of pervasive transcripts originating from multiple genomic regulatory features

View ORCID ProfileJoshua W. Collins, Daniel Martin, Genomics and Computational Biology Core, View ORCID ProfileShaohe Wang, View ORCID ProfileKenneth M. Yamada
doi: https://doi.org/10.1101/2021.01.29.428898
Joshua W. Collins
1Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, 20892, USA
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  • For correspondence: joshua.collins@nih.gov kenneth.yamada@nih.gov
Daniel Martin
2National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, 20892, USA
3Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, 20892, USA
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3Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, 20892, USA
Shaohe Wang
1Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, 20892, USA
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Kenneth M. Yamada
1Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, 20892, USA
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  • For correspondence: joshua.collins@nih.gov kenneth.yamada@nih.gov
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ABSTRACT

The vast majority of mammalian genomes are transcribed as non-coding RNA in what is referred to as “pervasive transcription.” Recent studies have uncovered various families of non-coding RNA transcribed upstream of transcription start sites. In particular, highly unstable promoter upstream transcripts known as PROMPTs have been shown to be targeted for exosomal degradation by the nuclear exosome targeting complex (NEXT) consisting of the RNA helicase MTR4, the zinc-knuckle scaffold ZCCHC8, and the RNA binding protein RBM7. Here, we report that in addition to its known RNA substrates, ZCCHC8 is required for the targeted degradation of pervasive transcripts produced at CTCF binding sites, open chromatin regions, promoters, promoter flanking regions, and transcription factor binding sites. Additionally, we report that a significant number of RIKEN cDNAs and predicted genes display the hallmarks of PROMPTs and are also substrates for ZCCHC8 and/or NEXT complex regulation suggesting these are unlikely to be functional genes. Our results suggest that ZCCHC8 and/or the NEXT complex may play a larger role in the global regulation of pervasive transcription than previously reported.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Updated Acknowledgments to include all members of Genomics and Computational Biology Core.

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse165689

  • https://github.com/collinsjw/Zcchc8-KO-pervasive-transcripts

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 06, 2021.
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ZCCHC8 is required for the degradation of pervasive transcripts originating from multiple genomic regulatory features
Joshua W. Collins, Daniel Martin, Genomics and Computational Biology Core, Shaohe Wang, Kenneth M. Yamada
bioRxiv 2021.01.29.428898; doi: https://doi.org/10.1101/2021.01.29.428898
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ZCCHC8 is required for the degradation of pervasive transcripts originating from multiple genomic regulatory features
Joshua W. Collins, Daniel Martin, Genomics and Computational Biology Core, Shaohe Wang, Kenneth M. Yamada
bioRxiv 2021.01.29.428898; doi: https://doi.org/10.1101/2021.01.29.428898

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