Nuclear speckles are nuclear condensates also known as interchromatin granule clusters. These condensates are enriched in pre-mRNA splicing factors located in the interchromatin region of the nucleoplasm.
Useful reviews: 31394307, 33337476, 34245118, 28977640).
Formation, Composition & dynamics (Assembly and disassembly)
Relation to human diseases
Proteome
Formation, Composition & dynamics (Assembly and disassembly)
The spliceosomal snRNAs and numerous related protein factors that form the snRNPs are among the constituents of the nuclear speckle, and they play a role in pre-mRNA splicing. Heteronuclear RNPs (hnRNPs), cleavage and polyadenylation factors, protein kinases including CDC-like kinase (CLK), components of the exon junction complex (EJC), and structural proteins are among the other constituents. The long non-coding RNA (ncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and polyadenylated (poly(A)+) RNA are two of the most common RNAs in nuclear speckles (reviewed in 24040563).
33095160 showed that the core of nuclear speckle is likely generated by SON and SRRM2, because depletion of SON causes only a partial disassembly of nuclear speckle, but depletion of SON in a cell-line with intrinsically disordered regions (IDRs) of SRRM2 causes a near-complete dissolution of nuclear speckle.
Relation to human diseases
Nuclear speckles are described to be linked to different types of cancer (30244836, 27238081), neurological disorders (28977640, 24040563, obesity (24627050) and HIV (32665593).
Proteome
10428969 and 15169873 purified nuclear speckles proteins using mass spectrometry.
References
Chen Y, Belmont AS. Genome organization around nuclear speckles. Curr Opin Genet Dev. 2019 Apr;55:91-99. doi: 10.1016/j.gde.2019.06.008. Epub 2019 Aug 5. PMID: 31394307; PMCID: PMC6759399.
Liao SE, Regev O. Splicing at the phase-separated nuclear speckle interface: a model. Nucleic Acids Res. 2021 Jan 25;49(2):636-645. doi: 10.1093/nar/gkaa1209. PMID: 33337476; PMCID: PMC7826271.
Ilık İA, Aktaş T. Nuclear speckles: dynamic hubs of gene expression regulation. FEBS J. 2021 Jul 10. doi: 10.1111/febs.16117. Epub ahead of print. PMID: 34245118.
Galganski L, Urbanek MO, Krzyzosiak WJ. Nuclear speckles: molecular organization, biological function and role in disease. Nucleic Acids Res. 2017 Oct 13;45(18):10350-10368. doi: 10.1093/nar/gkx759. PMID: 28977640; PMCID: PMC5737799.
Morimoto M, Boerkoel CF. The role of nuclear bodies in gene expression and disease. Biology (Basel). 2013 Jul 9;2(3):976-1033. doi: 10.3390/biology2030976. PMID: 24040563; PMCID: PMC3771687.
Ilik İA, Malszycki M, Lübke AK, Schade C, Meierhofer D, Aktaş T. SON and SRRM2 are essential for nuclear speckle formation. Elife. 2020 Oct 23;9:e60579. doi: 10.7554/eLife.60579. PMID: 33095160; PMCID: PMC7671692.
Bouchard JJ, Otero JH, Scott DC, Szulc E, Martin EW, Sabri N, Granata D, Marzahn MR, Lindorff-Larsen K, Salvatella X, Schulman BA, Mittag T. Cancer Mutations of the Tumor Suppressor SPOP Disrupt the Formation of Active, Phase-Separated Compartments. Mol Cell. 2018 Oct 4;72(1):19-36.e8. doi: 10.1016/j.molcel.2018.08.027. Epub 2018 Sep 20. PMID: 30244836; PMCID: PMC6179159.
Groner AC, Cato L, de Tribolet-Hardy J, Bernasocchi T, Janouskova H, Melchers D, Houtman R, Cato ACB, Tschopp P, Gu L, Corsinotti A, Zhong Q, Fankhauser C, Fritz C, Poyet C, Wagner U, Guo T, Aebersold R, Garraway LA, Wild PJ, Theurillat JP, Brown M. TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer. Cancer Cell. 2016 Jun 13;29(6):846-858. doi: 10.1016/j.ccell.2016.04.012. Epub 2016 May 26. PMID: 27238081; PMCID: PMC5124371.
Zhao X, Yang Y, Sun BF, Zhao YL, Yang YG. FTO and obesity: mechanisms of association. Curr Diab Rep. 2014;14(5):486. doi: 10.1007/s11892-014-0486-0. PMID: 24627050.
Francis AC, Marin M, Singh PK, Achuthan V, Prellberg MJ, Palermino-Rowland K, Lan S, Tedbury PR, Sarafianos SG, Engelman AN, Melikyan GB. HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains. Nat Commun. 2020 Jul 14;11(1):3505. doi: 10.1038/s41467-020-17256-8. Erratum in: Nat Commun. 2020 Nov 26;11(1):6165. PMID: 32665593; PMCID: PMC7360574.
Mintz PJ, Patterson SD, Neuwald AF, Spahr CS, Spector DL. Purification and biochemical characterization of interchromatin granule clusters. EMBO J. 1999 Aug 2;18(15):4308-20. doi: 10.1093/emboj/18.15.4308. PMID: 10428969; PMCID: PMC1171507.
Saitoh N, Spahr CS, Patterson SD, Bubulya P, Neuwald AF, Spector DL. Proteomic analysis of interchromatin granule clusters. Mol Biol Cell. 2004 Aug;15(8):3876-90. doi: 10.1091/mbc.e04-03-0253. Epub 2004 May 28. PMID: 15169873; PMCID: PMC491843.