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

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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.
Translated title of the contributionTuman aktiinin interatomi liittää aktiinin KAT14 histoniasetylaatiotranferaasin toimintaan ja mRNA:n silmukointiin.
Original languageEnglish
JournalJournal of Cell Science
Volume132
Issue number8
ISSN0021-9533
Publication statusPublished - 17 Apr 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology

Cite this

@article{52f8924599174d7e83e49bbc76aae38e,
title = "Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing.",
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 = "1182 Biochemistry, cell and molecular biology, Nucleus, Actin, histone acetyltransferase (HAT), mRNA splicing",
author = "Tiina Viita and Salla Kyher{\"o}inen and Bina Prajapati and Jori Virtanen and Mikko Frilander and Markku Varjosalo and Maria Vartiainen",
year = "2019",
month = "4",
day = "17",
language = "English",
volume = "132",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "8",

}

TY - JOUR

T1 - Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing.

AU - Viita, Tiina

AU - Kyheröinen, Salla

AU - Prajapati, Bina

AU - Virtanen, Jori

AU - Frilander, Mikko

AU - Varjosalo, Markku

AU - Vartiainen, Maria

PY - 2019/4/17

Y1 - 2019/4/17

N2 - 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.

AB - 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.

KW - 1182 Biochemistry, cell and molecular biology

KW - Nucleus

KW - Actin

KW - histone acetyltransferase (HAT)

KW - mRNA splicing

M3 - Article

VL - 132

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 8

ER -