Genome organization around nuclear speckles drives mRNA splicing efficiency

  • Bhat, P., Honson, D. & Guttman, M. Nuclear compartmentalization as a mechanism of quantitative control of gene expression. Nat. Rev. Mol. Cell Biol. 22, 653–670 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dundr, M. & Misteli, T. Biogenesis of nuclear bodies. Cold Spring Harb. Perspect. Biol. https://doi.org/10.1101/cshperspect.a000711 (2010).

  • Spector, D. L. & Lamond, A. I. Nuclear speckles. Cold Spring Harb. Perspect. Biol. 3, a000646 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mattaj, I. W. Splicing in space. Nature https://doi.org/10.1038/372727a0 (1994).

  • Lewis, J. D. & Tollervey, D. Like attracts like: getting RNA processing together in the nucleus. Science 288, 1385–1389 (2000).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Shachar, S. & Misteli, T. Causes and consequences of nuclear gene positioning. J. Cell Sci. 130, 1501–1508 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Belmont, A. S. Nuclear compartments: an incomplete primer to nuclear compartments, bodies, and genome organization relative to nuclear architecture. Cold Spring Harb. Perspect. Biol. 14, a041268 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Putnam, A., Thomas, L. & Seydoux, G. RNA granules: functional compartments or incidental condensates? Genes Dev. 37, 354–376 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Herzel, L., Ottoz, D. S. M., Alpert, T. & Neugebauer, K. M. Splicing and transcription touch base: co-transcriptional spliceosome assembly and function. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/nrm.2017.63 (2017).

  • Maquat, L. E. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat. Rev. Mol. Cell Biol. 5, 89–99 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Scotti, M. M. & Swanson, M. S. RNA mis-splicing in disease. Nat. Rev. Genet. 17, 19–32 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Huang, S. & Spector, D. L. U1 and U2 small nuclear RNAs are present in nuclear speckles. Proc. Natl Acad. Sci. USA 89, 305–308 (1992).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fu, X. D. & Maniatis, T. Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus. Nature 343, 437–441 (1990).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Spector, D. L., Schrier, W. H. & Busch, H. Immunoelectron microscopic localization of snRNPs. Biol. Cell 49, 1–10 (1983).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lerner, E. A., Lerner, M. R., Janeway, C. A. J. & Steitz, J. A. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc. Natl Acad. Sci. USA 78, 2737–2741 (1981).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hall, L. L., Smith, K. P., Byron, M. & Lawrence, J. B. Molecular anatomy of a speckle. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. https://doi.org/10.1002/ar.a.20336 (2006).

  • Cmarko, D. et al. Ultrastructural analysis of transcription and splicing in the cell nucleus after bromo-UTP microinjection. Mol. Biol. Cell 10, 211–223 (1999).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fakan, S., Leser, G. & Martin, T. E. Ultrastructural distribution of nuclear ribonucleoproteins as visualized by immunocytochemistry on thin sections. J. Cell Biol. 98, 358–363 (1984).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, G., Taneja, K. L., Singer, R. H. & Green, M. R. Localization of pre-mRNA splicing in mammalian nuclei. Nature 372, 809–812 (1994).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Huang, S., Deerinck, T. J., Ellisman, M. H. & Spector, D. L. In vivo analysis of the stability and transport of nuclear poly(A)+ RNA. J. Cell Biol. 126, 877–899 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • 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 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Jiménez-García, L. F. & Spector, D. L. In vivo evidence that transcription and splicing are coordinated by a recruiting mechanism. Cell 73, 47–59 (1993).

    Article 
    PubMed 

    Google Scholar
     

  • Sacco-Bubulya, P. & Spector, D. L. Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing. J. Cell Biol. 156, 425–436 (2002).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Misteli, T. & Spector, D. L. Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors. Mol. Biol. Cell 7, 1559–1572 (1996).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 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
     

  • Misteli, T. & Spector, D. L. RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo. Mol. Cell 3, 697–705 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xie, S. Q., Martin, S., Guillot, P. V., Bentley, D. L. & Pombo, A. Splicing speckles are not reservoirs of RNA polymerase II, but contain an inactive form, phosphorylated on serine2 residues of the C-terminal domain. Mol. Biol. Cell 17, 1723–1733 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Misteli, T. et al. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. J. Cell Biol. 143, 297–307 (1998).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tammer, L. et al. Gene architecture directs splicing outcome in separate nuclear spatial regions. Mol. Cell 82, 1021–1034.e8 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barutcu, A. R. et al. Systematic mapping of nuclear domain-associated transcripts reveals speckles and lamina as hubs of functionally distinct retained introns. Mol. Cell 82, 1035–1052.e9 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, K. et al. Intronless mRNAs transit through nuclear speckles to gain export competence. J. Cell Biol. 217, 3912–3929 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, J., Venkata, N. C., Hernandez Gonzalez, G. A., Khanna, N. & Belmont, A. S. Gene expression amplification by nuclear speckle association. J. Cell Biol. 219, e201904046 (2020).

    PubMed 

    Google Scholar
     

  • Zhong, X.-Y., Wang, P., Han, J., Rosenfeld, M. G. & Fu, X.-D. SR proteins in vertical integration of gene expression from transcription to RNA processing to translation. Mol. Cell 35, 1–10 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lawrence, J. B. & Clemson, C. M. Gene associations: true romance or chance meeting in a nuclear neighborhood? J. Cell Biol. 182, 1035–1038 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Perraud, M., Gioud, M. & Monier, J. C. [Intranuclear structures of monkey kidney cells recognised by immunofluorescence and immuno-electron microscopy using anti-ribonucleoprotein antibodies (author’s transl)]. Ann. Immunol. 130C, 635–647 (1979).

    CAS 

    Google Scholar
     

  • Chen, Y. et al. Mapping 3D genome organization relative to nuclear compartments using TSA-seq as a cytological ruler. J. Cell Biol. 217, 4025–4048 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quinodoz, S. A. et al. Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus. Cell 174, 744–757.e24 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Takei, Y. et al. Integrated spatial genomics reveals global architecture of single nuclei. Nature 590, 344–350 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quinodoz, S. A. et al. RNA promotes the formation of spatial compartments in the nucleus. Cell 184, 5775–5790.e30 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wilkinson, M. E., Charenton, C. & Nagai, K. RNA splicing by the spliceosome. Annu. Rev. Biochem. 89, 359–388 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Will, C. L. & Lührmann, R. Spliceosome structure and function. Cold Spring Harb. Perspect. Biol. 3, a003707 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Calvet, J. P. & Pederson, T. Base-pairing interactions between small nuclear RNAs and nuclear RNA precursors as revealed by psoralen cross-linking in vivo. Cell 26, 363–370 (1981).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Engreitz, J. M. et al. RNA–RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159, 188–199 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wuarin, J. & Schibler, U. Physical isolation of nascent RNA chains transcribed by RNA polymerase II: evidence for cotranscriptional splicing. Mol. Cell. Biol. 14, 7219–7225 (1994).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goronzy, I. N. et al. Simultaneous mapping of 3D structure and nascent RNAs argues against nuclear compartments that preclude transcription. Cell Rep. 41, 111730 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Takei, Y. et al. Single-cell nuclear architecture across cell types in the mouse brain. Science 374, 586–594 (2021).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, L. et al. TSA-seq reveals a largely conserved genome organization relative to nuclear speckles with small position changes tightly correlated with gene expression changes. Genome Res. 31, 251–264 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pichon, X., Robert, M.-C., Bertrand, E., Singer, R. H. & Tutucci, E. New generations of MS2 variants and MCP fusions to detect single mRNAs in living eukaryotic cells. Methods Mol. Biol. 2166, 121–144 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tripathi, V. et al. SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles. Mol. Biol. Cell 23, 3694–3706 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ilık, İ. A. et al. SON and SRRM2 are essential for nuclear speckle formation. eLife 9, e60579 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Thul, P. J. et al. A subcellular map of the human proteome. Science 356, eaal3321 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Olins, A. L., Rhodes, G., Welch, D. B. M., Zwerger, M. & Olins, D. E. Lamin B receptor: multi-tasking at the nuclear envelope. Nucleus 1, 53–70 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reed, R. & Maniatis, T. A role for exon sequences and splice-site proximity in splice-site selection. Cell 46, 681–690 (1986).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Szymczyna, B. R. et al. Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing. Genes Dev. 17, 461–475 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quinodoz, S. A. & Guttman, M. Essential roles for RNA in shaping nuclear organization. Cold Spring Harb. Perspect. Biol. 14, a039719 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McCracken, S. et al. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature 385, 357–360 (1997).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Ding, F. & Elowitz, M. B. Constitutive splicing and economies of scale in gene expression. Nat. Struct. Mol. Biol. 26, 424–432 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yuryev, A. et al. The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins. Proc. Natl Acad. Sci. USA 93, 6975–6980 (1996).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lazarev, D. & Manley, J. L. Concurrent splicing and transcription are not sufficient to enhance splicing efficiency. RNA 13, 1546–1557 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zimber, A., Nguyen, Q.-D. & Gespach, C. Nuclear bodies and compartments: functional roles and cellular signalling in health and disease. Cell Signal. 16, 1085–1104 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Quinodoz, S. A. et al. SPRITE: a genome-wide method for mapping higher-order 3D interactions in the nucleus using combinatorial split-and-pool barcoding. Nat. Protoc. 17, 36–75 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Banerjee, A. K. et al. SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses. Cell 183, 1325–1339.e21 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Melsted, P. et al. Modular, efficient and constant-memory single-cell RNA-seq preprocessing. Nat. Biotechnol. 39, 813–818 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Engreitz, J. M. et al. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 539, 452–455 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, S. et al. Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science 360, 176–182 (2018).

    Article 
    ADS 

    Google Scholar
     

  • Huang, S. et al. Mapping and modeling the genomic basis of differential RNA isoform expression at single-cell resolution with LR-Split-seq. Genome Biol. 22, 286 (2021).

    Article 

    Google Scholar
     

  • Majumdar, D. S. et al. Programmed delayed splicing: a mechanism for timed inflammatory gene expression. Preprint at bioRxiv https://doi.org/10.1101/443796 (2018).

  • Mayr, C. & Bartel, D. P. Widespread shortening of 3′ UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138, 673–684 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Manna, P. T., Davis, L. J. & Robinson, M. S. Fast and cloning-free CRISPR/Cas9-mediated genomic editing in mammalian cells. Traffic 20, 974–982 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Raj, A., van den Bogaard, P., Rifkin, S. A., van Oudenaarden, A. & Tyagi, S. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods 5, 877–879 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stringer, C., Wang, T., Michaelos, M. & Pachitariu, M. Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods 18, 100–106 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     


  • Source link

    Total
    0
    Shares
    Leave a Reply

    Your email address will not be published. Required fields are marked *

    Related Posts