Monoallelically-expressed Noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression

  1. Qinyu Hao
  2. Minxue Liu
  3. Swapna Vidhur Daulatabad
  4. Saba Gaffari
  5. You Jin Song
  6. Rajneesh Srivastava
  7. Shivang Bhaskar
  8. Anurupa Moitra
  9. Hazel Mangan
  10. Elizabeth Tseng
  11. Rachel B Gilmore
  12. Susan M Frier
  13. Xin Chen
  14. Chengliang Wang
  15. Sui Huang
  16. Stormy Chamberlain
  17. Hong Jin
  18. Jonas Korlach
  19. Brian McStay
  20. Saurabh Sinha
  21. Sarath C Janga
  22. Supriya Prasanth
  23. Kannanganattu V Prasanth  Is a corresponding author
  1. University of Illinois Urbana-Champaign, United States
  2. Indiana University - Purdue University Indianapolis, United States
  3. National University of Ireland, Galway, Ireland
  4. Pacific Biosciences, United States
  5. University of Connecticut Health Center, United States
  6. Ionis Pharmaceuticals, United States
  7. Northwestern University, United States

Abstract

Out of the several hundred copies of rRNA genes arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ~50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to the differential expression of rRNAs. However, the mechanism(s) controlling the dosage of active versus inactive rRNA genes within each NOR in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influence rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosomes. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs influencing rRNA expression by forming constrained nucleolar territories on individual NORs.

Data availability

Sequencing data have been deposited in NCBI SRA data base under accession code PRJNA814414

The following data sets were generated

Article and author information

Author details

  1. Qinyu Hao

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  2. Minxue Liu

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  3. Swapna Vidhur Daulatabad

    Department of BioHealth Informatics, Indiana University - Purdue University Indianapolis, Indianapolis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5288-8599
  4. Saba Gaffari

    Department of Computer Science, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  5. You Jin Song

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  6. Rajneesh Srivastava

    Department of BioHealth Informatics, Indiana University - Purdue University Indianapolis, Indianapolis,, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1093-2082
  7. Shivang Bhaskar

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  8. Anurupa Moitra

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  9. Hazel Mangan

    Centre for Chromosome Biology, National University of Ireland, Galway, Galway, Ireland
    Competing interests
    No competing interests declared.
  10. Elizabeth Tseng

    Pacific Biosciences, San Fransisco, United States
    Competing interests
    Elizabeth Tseng, is affiliated with Pacific Biosciences. The author has no financial interests to declare.
  11. Rachel B Gilmore

    Department of Genetics and Genome Sciences, University of Connecticut Health Center, Connecticut, United States
    Competing interests
    No competing interests declared.
  12. Susan M Frier

    Ionis Pharmaceuticals, Carlsbad, United States
    Competing interests
    Susan M Frier, is affiliated with Ionis Pharmaceuticals Inc. The author has no financial interests to declare..
  13. Xin Chen

    Department of Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  14. Chengliang Wang

    Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  15. Sui Huang

    Department of Cell and Molecular Biology, Northwestern University, Chicago, United States
    Competing interests
    No competing interests declared.
  16. Stormy Chamberlain

    Department of Genetics and Genome Sciences, University of Connecticut Health Center, Connecticut, United States
    Competing interests
    No competing interests declared.
  17. Hong Jin

    Department of Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  18. Jonas Korlach

    Pacific Biosciences, Menlo park, United States
    Competing interests
    Jonas Korlach, is affiliated with Pacific Biosciences. The author has no financial interests to declare.
  19. Brian McStay

    Centre for Chromosome Biology, National University of Ireland, Galway, Galway, Ireland
    Competing interests
    No competing interests declared.
  20. Saurabh Sinha

    Department of Computer Science, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
  21. Sarath C Janga

    Department of BioHealth Informatics, Indiana University - Purdue University Indianapolis, Indianapolis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7351-6268
  22. Supriya Prasanth

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3735-7498
  23. Kannanganattu V Prasanth

    Department of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, United States
    For correspondence
    kumarp@illinois.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4587-8362

Funding

National Institute of General Medical Sciences (GM132458)

  • Kannanganattu V Prasanth

National Science Foundation (2225264)

  • Supriya Prasanth

National Science Foundation (1940422)

  • Sarath C Janga

National Science Foundation (1908992)

  • Sarath C Janga

National Institute of General Medical Sciences (GM120552)

  • Hong Jin

National Institute on Aging (AG065748)

  • Kannanganattu V Prasanth

National Institute of General Medical Sciences (GM125196)

  • Supriya Prasanth

National Institute of General Medical Sciences (R35GM131819)

  • Saurabh Sinha

National Institute on Aging (R21AG065748)

  • Sarath C Janga

National Institute of General Medical Sciences (R01GM123314)

  • Sarath C Janga

National Science Foundation (1723008)

  • Kannanganattu V Prasanth

National Science Foundation (1243372)

  • Supriya Prasanth

National Science Foundation (1818286)

  • Supriya Prasanth

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jeannie T Lee, Massachusetts General Hospital, United States

Version history

  1. Received: May 31, 2022
  2. Preprint posted: July 4, 2022 (view preprint)
  3. Accepted: January 18, 2024
  4. Accepted Manuscript published: January 19, 2024 (version 1)
  5. Version of Record published: February 8, 2024 (version 2)

Copyright

© 2024, Hao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Qinyu Hao
  2. Minxue Liu
  3. Swapna Vidhur Daulatabad
  4. Saba Gaffari
  5. You Jin Song
  6. Rajneesh Srivastava
  7. Shivang Bhaskar
  8. Anurupa Moitra
  9. Hazel Mangan
  10. Elizabeth Tseng
  11. Rachel B Gilmore
  12. Susan M Frier
  13. Xin Chen
  14. Chengliang Wang
  15. Sui Huang
  16. Stormy Chamberlain
  17. Hong Jin
  18. Jonas Korlach
  19. Brian McStay
  20. Saurabh Sinha
  21. Sarath C Janga
  22. Supriya Prasanth
  23. Kannanganattu V Prasanth
(2024)
Monoallelically-expressed Noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression
eLife 13:e80684.
https://doi.org/10.7554/eLife.80684

Share this article

https://doi.org/10.7554/eLife.80684

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