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J Cell Sci. 2019 Apr 17;132(8). pii: jcs226852. doi: 10.1242/jcs.226852.

Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing.

Author information

1
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
2
Helsinki Institute of Life Science, University of Helsinki, Helsinki 00014, Finland.
3
Proteomics Unit, University of Helsinki, Helsinki 00014, Finland.
4
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland maria.vartiainen@helsinki.fi.

Abstract

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.

KEYWORDS:

Actin; Histone acetyl transferase; Nucleus; Pre-mRNA processing; Transcription; hATAC

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