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
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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