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  SON and SRRM2 are essential for nuclear speckle formation

Ilik, I. A., Malszycki, M., Lübke, A. K., Schade, C., Meierhofer, D., & Aktas, T. (2020). SON and SRRM2 are essential for nuclear speckle formation. eLife, 2020(9): e60579. doi:10.7554/eLife.60579.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-51D2-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-B8E6-6
Genre: Journal Article

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 Creators:
Ilik, Ibrahim Avsar1, Author              
Malszycki, Michal1, Author              
Lübke, Anna Katharina1, Author              
Schade, Claudia1, Author              
Meierhofer, David2, Author              
Aktas, Tugce1, Author              
Affiliations:
1Quantitative RNA Biology (Tugce Aktas), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014184              
2Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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 Abstract: The nucleus of higher eukaryotes is a highly compartmentalized and dynamic organelle consisting of several biomolecular condensates that regulate gene expression at multiple levels (Banani et al., 2017; Shin and Brangwynne, 2017). First reported more than 100 years ago by Ramón y Cajal, nuclear speckles (NS) are among the most prominent of such condensates (Spector and Lamond, 2011). Despite their prevalence, research on the function of NS is virtually restricted to colocalization analyses, since an organizing core, without which NS cannot form, remains unidentified (Chen and Belmont, 2019; Galganski et al., 2017). The monoclonal antibody SC35, which was raised against a spliceosomal extract, is a frequently used reagent to mark NS since its debut in 1990 (Fu and Maniatis, 1990). Unexpectedly, we found that this antibody has been misidentified and the main target of SC35 mAb is SRRM2, a large (~300 kDa), spliceosome-associated (Jia and Sun, 2018) protein with prominent intrinsically disordered regions (IDRs) that sharply localizes to NS (Blencowe et al., 1994). Here we show that, the core of NS is likely formed by SON and SRRM2, since depletion of SON leads only to a partial disassembly of NS as reported previously (Ahn et al., 2011; Fei et al., 2017; Sharma et al., 2010), in contrast, combined depletion of SON together with SRRM2, but not other NS associated factors, or depletion of SON in a cell line where IDRs of SRRM2 are genetically deleted, leads to a near-complete dissolution of NS. This work, therefore, paves the way to study the role of NS under diverse physiological and stress conditions.

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Language(s): eng - English
 Dates: 2020-10-202020-10-23
 Publication Status: Published online
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 Identifiers: DOI: 10.7554/eLife.60579
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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 2020 (9) Sequence Number: e60579 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X