Editing Cell nucleus (section)

==={{anchor|Splicing speckles}} Splicing speckles===

Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells.<ref>
{{cite journal | vauthors = Spector DL, Lamond AI | title = Nuclear speckles | journal = Cold Spring Harbor Perspectives in Biology | volume = 3 | issue = 2 | pages = a000646 | date = Feb 2011 | pmid = 20926517 | pmc = 3039535 | doi = 10.1101/cshperspect.a000646 | department = Review }}</ref>
At the fluorescence-microscope level they appear as irregular, punctate structures, which vary in size and shape, and when examined by electron microscopy they are seen as clusters of [[interchromatin granules]]. Speckles are dynamic structures, and both their protein and RNA-protein components can cycle continuously between speckles and other nuclear locations, including active transcription sites. Speckles can work with [[p53]] as enhancers of gene activity to directly enhance the activity of certain genes. Moreover, speckle-associating and non-associating p53 gene targets are functionally distinct.<ref>
{{cite journal | vauthors = Alexander KA, Coté A, Nguyen SC, Zhang L, Berger SL | title = p53 mediates target gene association with nuclear speckles for amplified RNA expression | journal = Molecular Cell | volume =  81| issue =  8| pages = S1097-2765(21)00174-X | date = Mar 2021 | pmid = 33823140 | pmc =  8830378| doi = 10.1016/j.molcel.2021.03.006 | s2cid = 233172170 | department = Primary }}</ref>

Studies on the composition, structure and behaviour of speckles have provided a model for understanding the functional compartmentalization of the nucleus and the organization of the gene-expression machinery<ref name="ReferenceA">{{cite journal | vauthors = Lamond AI, Spector DL | title = Nuclear speckles: a model for nuclear organelles | journal = Nature Reviews. Molecular Cell Biology | volume = 4 | issue = 8 | pages = 605–12 | date = August 2003 | pmid = 12923522 | doi = 10.1038/nrm1172 | s2cid = 6439413 | department = Review }}</ref> splicing [[snRNP]]s<ref>{{cite journal | vauthors = Tripathi K, Parnaik VK | title = Differential dynamics of splicing factor SC35 during the cell cycle | journal = Journal of Biosciences | volume = 33 | issue = 3 | pages = 345–54 | date = September 2008 | pmid = 19005234 | doi = 10.1007/s12038-008-0054-3 | url = http://www.ias.ac.in/jbiosci/sep2008/345.pdf | url-status = live | s2cid = 6332495 | department = Primary | archive-url = https://web.archive.org/web/20111115235056/http://www.ias.ac.in/jbiosci/sep2008/345.pdf | archive-date = 15 November 2011 }}</ref><ref>{{cite journal | vauthors = Tripathi K, Parnaik VK | title = Differential dynamics of splicing factor SC35 during the cell cycle | journal = Journal of Biosciences | volume = 33 | issue = 3 | pages = 345–54 | date = September 2008 | pmid = 19005234 | doi = 10.1007/s12038-008-0054-3 | s2cid = 6332495 | department = Primary }}</ref> and other splicing proteins necessary for pre-mRNA processing.<ref name="ReferenceA"/> Because of a cell's changing requirements, the composition and location of these bodies changes according to mRNA transcription and regulation via [[phosphorylation]] of specific proteins.<ref name="Handwerger">{{cite journal | vauthors = Handwerger KE, Gall JG | title = Subnuclear organelles: new insights into form and function | journal = Trends in Cell Biology | volume = 16 | issue = 1 | pages = 19–26 | date = January 2006 | pmid = 16325406 | doi = 10.1016/j.tcb.2005.11.005 | department = Review }}</ref> The splicing speckles are also known as nuclear speckles (nuclear specks), splicing factor compartments (SF compartments), interchromatin granule clusters (IGCs), and [[snurposome|B snurposomes]].<ref>{{cite web | title = Cellular component Nucleus speckle | publisher = UniProt: UniProtKB | url = https://www.uniprot.org/locations/SL-0186 | access-date = 30 August 2013}}</ref>
B snurposomes are found in the amphibian oocyte nuclei and in ''[[Drosophila melanogaster]]'' embryos. B snurposomes appear alone or attached to the Cajal bodies in the electron micrographs of the amphibian nuclei.<ref>
{{cite journal | vauthors = Gall JG, Bellini M, Wu Z, Murphy C | title = Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes | journal = Molecular Biology of the Cell | volume = 10 | issue = 12 | pages = 4385–402 | date = December 1999 | pmid = 10588665 | pmc = 25765 | doi = 10.1091/mbc.10.12.4385 | department = Primary }}</ref> While nuclear speckles were originally thought to be storage sites for the splicing factors,<ref name="Matera2007_NatureMolCellBio">{{cite journal | vauthors = Matera AG, Terns RM, Terns MP | title = Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 3 | pages = 209–20 | date = March 2007 | pmid = 17318225 | doi = 10.1038/nrm2124 | s2cid = 30268055 | department = Review }}</ref> a more recent study demonstrated that organizing genes and pre-mRNA substrates near speckles increases the kinetic efficiency of pre-mRNA splicing, ultimately boosting protein levels by modulation of splicing.<ref>{{cite journal | vauthors = Bhat P, Chow A, Emert B et al | title = Genome organization around nuclear speckles drives mRNA splicing efficiency. | journal = Nature | volume = 629 | issue = 5 | pages = 1165–1173 | date = May 2024 | pmid = 38720076 | pmc = 11164319 | doi = 10.1038/s41586-024-07429-6 | bibcode = 2024Natur.629.1165B }}</ref>