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Nucleation of nuclear bodies by RNA

Nature Cell Biology volume 13, pages 167–173 (2011)Cite this article

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Abstract

The biogenesis of the many functional compartments contained in the mammalian cell nucleus is poorly understood. More specifically, little is known regarding the initial nucleation step required for nuclear body formation. Here we show that RNA can function as a structural element and a nucleator of nuclear bodies. We find that several types of coding and noncoding RNAs are sufficient to de novo assemble, and are physiologically enriched in, histone locus bodies (with associated Cajal bodies), nuclear speckles, paraspeckles and nuclear stress bodies. Formation of nuclear bodies occurs through recruitment and accumulation of proteins resident in the nuclear bodies by nucleating RNA. These results demonstrate that transcription is a driving force in nuclear body formation and RNA transcripts can function as a scaffold in the formation of major nuclear bodies. Together, these data suggest that RNA-primed biogenesis of nuclear bodies is a general principle of nuclear organization.

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Figure 1: Immobilization of histone pre-mRNA to chromatin leads to formation of a HLB with associated Cajal body.
Figure 2: Live-cell 4D imaging of de novo Cajal body formation nucleated by non-cleavable histone H2b–MS2 transcripts and de novo formation of HLB and Cajal body by factors involved in histone gene expression and histone 3′ end processing.
Figure 3: Tethering spliced β-globin–MS2 pre-mRNA on chromatin leads to association with splicing speckle or de novo formation of nuclear speckle.
Figure 4: Tethering noncoding NEAT1 RNA leads to formation of a de novo paraspeckle.
Figure 5: Immobilization of the noncoding satIII transcripts on chromatin, without heat-shock induction, leads to formation of nSB.

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References

  1. Lamond, A. I. & Spector, D. L. Nuclear speckles: a model for nuclear organelles. Nat. Rev. Mol. Cell Biol. 4, 605–612 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Handwerger, K. E. & Gall, J. G. Subnuclear organelles: new insights into form and function. Trends Cell Biol. 16, 19–26 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Misteli, T. Beyond the sequence: cellular organization of genome function. Cell 128, 787–800 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Shaw, P. J. & Jordan, E. G. The nucleolus. Annu. Rev. Cell Dev. Biol. 11, 93–121 (1995).

    Article  CAS  PubMed  Google Scholar 

  5. Bongiorno-Borbone, L. et al. FLASH and NPAT positive but not Coilin positive Cajal bodies correlate with cell ploidy. Cell Cycle 7, 2357–2367 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Misteli, T., Cáceres, J. F. & Spector D. L. The dynamics of a pre-mRNA splicing factor in living cells. Nature 387, 523–527 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Hall L. L., Smith, K. P., Byron, M. & Lawrence, J. B. Molecular anatomy of a speckle. Anat. Rec. A. Discov. Mol. Cell Evol. Biol. 288, 664–675 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Valgardsdottir, R. et al. Structural and functional characterization of noncoding repetitive RNAs transcribed in stressed human cells. Mol. Biol. Cell 16, 2597–2604 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Clemson, C. M. et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol. Cell 33, 717–726 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sasaki, Y. T. et al. MENε/β noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc. Natl Acad. Sci. USA. 106, 2525–2530 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sunwoo, H. et al. MEN ε/β nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res. 19, 347–359 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen, L.-L. & Carmichael, G. G. Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. Mol. Cell 35, 467–478 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kaiser, T. E., Intine, R. V. & Dundr, M. De novo formation of a subnuclear body. Science 322, 1713–1717 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Dundr, M. et al. Actin-dependent intranuclear repositioning of an active gene locus in vivo. J. Cell Biol. 179, 1095–1103 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Marzluff, W. F., Wagner, E. J. & Duronio, R. J. Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail. Nat. Rev. Genet. 9, 843–854 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cioce, M. & Lamond, A. I. Cajal bodies: a long history of discovery. Annu. Rev. Cell Dev. Biol. 21, 105–131 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Matera, A. G. et al. Nuclear bodies: random aggregates of sticky proteins or crucibles of macromolecular assembly? Dev. Cell 17, 639–647 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Erkmann, J. A. et al. Nuclear import of the stem-loop binding protein and localization during the cell cycle. Mol. Biol. Cell 16, 2960–2971 (2005).

    CAS  Google Scholar 

  19. Mandel, C. R., Bai, Y. & Tong, L. Protein factors in pre-mRNA 3′-end processing. Cell. Mol. Life. Sci. 65, 1099–1122 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Huang, S. & Spector, D. L. Intron-dependent recruitment of pre-mRNA splicing factors to sites of transcription. J. Cell Biol. 133, 719–732 (1996).

    Article  CAS  PubMed  Google Scholar 

  21. Biamonti, G. & Caceres, J. F. Cellular stress and RNA splicing. Trends Biochem. Sci. 34, 146–153 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Alastalo, T. P. et al. Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70. J. Cell Sci. 116, 3557–3570 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. Valgardsdottir, R. et al. Transcription of Satellite III non-coding RNAs is a general stress response in human cells. Nucleic Acids Res. 36, 423–434 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Frey, M. R. & Matera, A. G. RNA-mediated interaction of Cajal bodies and U2 snRNA genes. J. Cell Biol. 154, 499–509 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Carmo-Fonseca, M., Ferreira, J. & Lamond, A. I. Assembly of snRNP-containing coiled bodies is regulated in interphase and mitosis—evidence that the coiled body is a kinetic nuclear structure. J. Cell Biol. 120, 841–852 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. Bubulya, P. A. et al. Hypophosphorylated SR splicing factors transiently localize around active nucleolar organizing regions in telophase daughter nuclei. J. Cell Biol. 167, 51–63 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fox, A. H., Bond, C. S. & Lamond, A. I. P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner. Mol. Biol. Cell 16, 5304–5315 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Leung, A. K. et al. Quantitative kinetic analysis of nucleolar breakdown and reassembly during mitosis in live human cells. J. Cell Biol. 166, 787–800 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hu, Y. et al. Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template. J. Cell Biol. 185, 87–100 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank A. Belmont, M. Carmo-Fonseca, C. Clemson, V. De Laurenzi, A. Fox, J. Gall, M. Hastings, R. Intine, P. Kalab, A. Lamond, G. Matera, T. Misteli, D. Spector, E. Wagner and J. Zhao for reagents. We are particularly grateful to T. Misteli for helpful suggestions and critical reading of the manuscript and to V. Barr for help with the fast-spinning disc confocal microscope system. This research was supported by a Schweppe Career Development Award (the Schweppe Foundation) to M.D. and by startup funds from the Rosalind Franklin University of Medicine and Science to M.D.

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  1. Department of Cell Biology, Rosalind Franklin University of Medicine & Science, North Chicago, 60064, IL, USA

    Sergey P. Shevtsov & Miroslav Dundr

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  1. Sergey P. Shevtsov
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M.D. and S.P.S. conceived and designed the experiments. S.P.S. and M.D. performed the experiments and analysed the data. M.D. wrote the paper.

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Correspondence to Miroslav Dundr.

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Shevtsov, S., Dundr, M. Nucleation of nuclear bodies by RNA. Nat Cell Biol 13, 167–173 (2011). https://doi.org/10.1038/ncb2157

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