Open AccessNuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing
Author(s) -
Tiina Viita,
Salla Kyheröinen,
Bina Prajapati,
Jori Virtanen,
Mikko J. Frilander,
Markku Varjosalo,
Maria K. Vartiainen
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.226852
Subject(s) - biology , interactome , histone , microbiology and biotechnology , actin , rna splicing , actin remodeling , chromatin , minigene , cell nucleus , actin cytoskeleton , mdia1 , cytoskeleton , genetics , rna , nucleus , gene , cell
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.