Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing
Autor: | Bina Prajapati, Mikko J. Frilander, Jori Virtanen, Tiina Viita, Maria K. Vartiainen, Salla Kyheröinen, Markku Varjosalo |
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Přispěvatelé: | Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University Management, Molecular Systems Biology, Nuclear organization by actin, Machine learning in biomedicine |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
CHROMATIN
Transcriptional Activation RNA Splicing AFFINITY PURIFICATION PROTEIN Gene Expression macromolecular substances Biology Interactome Nucleus Mass Spectrometry Histone acetyl transferase 03 medical and health sciences 0302 clinical medicine hATAC Gene expression medicine Humans CRYSTAL-STRUCTURE Cytoskeleton Actin 030304 developmental biology Adaptor Proteins Signal Transducing Histone Acetyltransferases Cell Nucleus 0303 health sciences LEUCINE-RICH REPEAT F-ACTIN Alternative splicing Cell Biology ACETYLTRANSFERASE COMPLEX Chromatin Assembly and Disassembly GENE Actins Chromatin Cell biology Cell nucleus medicine.anatomical_structure Pre-mRNA processing RNA splicing 1182 Biochemistry cell and molecular biology HNRNP-U Transcription 030217 neurology & neurosurgery Research Article HeLa Cells |
Zdroj: | Journal of Cell Science |
ISSN: | 1477-9137 0021-9533 |
Popis: | In addition to its essential functions within the cytoskeleton, actin also localizes to the cell nucleus, where it is linked to many important nuclear processes from gene expression to maintenance of genomic integrity. However, the molecular mechanisms by which actin operates in the nucleus remain poorly understood. Here, we have used two complementary mass spectrometry (MS) techniques, AP-MS and BioID, to identify binding partners for nuclear actin. Common high-confidence interactions highlight the role of actin in chromatin-remodeling complexes and identify the histone-modifying complex human Ada-Two-A-containing (hATAC) as a novel actin-containing nuclear complex. Actin binds directly to the hATAC subunit KAT14, and modulates its histone acetyl transferase activity in vitro and in cells. Transient interactions detected through BioID link actin to several steps of transcription as well as to RNA processing. Alterations in nuclear actin levels disturb alternative splicing in minigene assays, likely by affecting the transcription elongation rate. This interactome analysis thus identifies both novel direct binding partners and functional roles for nuclear actin, as well as forms a platform for further mechanistic studies on how actin operates during essential nuclear processes. This article has an associated First Person interview with the first author of the paper. Highlighted Article: Nuclear actin interactome analysis reveals novel binding partners and functions for actin in the nucleus, with direct binding and regulation of the KAT14 HAT and functional link to pre-mRNA processing. |
Databáze: | OpenAIRE |
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