Modulating the expression of Chtop, a versatile regulator of gene-specific transcription and mRNA export

Keiichi Izumikawa; Hideaki Ishikawa; Richard J Simpson; Nobuhiro Takahashi

doi:10.1080/15476286.2018.1465795

Modulating the expression of Chtop, a versatile regulator of gene-specific transcription and mRNA export

RNA Biol. 2018;15(7):849-855. doi: 10.1080/15476286.2018.1465795. Epub 2018 May 11.

Authors

Keiichi Izumikawa¹, Hideaki Ishikawa¹, Richard J Simpson^{2

3}, Nobuhiro Takahashi^{1

2}

Affiliations

¹ a Department of Applied Biological Science , United Graduate School of Agriculture, Tokyo University of Agriculture and Technology , Fuchu , Tokyo , Japan.
² b Global Innovation Research Organizations, Tokyo University of Agriculture and Technology , Fuchu , Tokyo , Japan.
³ c La Trobe Institute for Molecular Science (LIMS) LIMS Building 1, Room 412 La Trobe University , Bundoora Victoria , Australia.

Abstract

Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export. The regulation of Chtop expression is, therefore, a key process during the expression of certain gene groups and pathogenesis of certain diseases. Our recent study revealed that cellular levels of Chtop are strictly autoregulated by a mechanism involving intron retention and nonsense-mediated mRNA decay. Here, we summarize roles of Chtop in gene-specific expression and highlight our recent findings concerning the autoregulation of Chtop.

Keywords: NMD; PRMT1; PRMT5; chtop; glioblastoma; intron retention; mRNA export; splicing; transcription; β-thalassemia.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Arginine / metabolism
Glioblastoma / metabolism*
Humans
Introns
Methylation
Mice
Nonsense Mediated mRNA Decay
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Protein-Arginine N-Methyltransferases / genetics
Protein-Arginine N-Methyltransferases / metabolism*
RNA Splicing
RNA, Messenger / genetics
RNA, Messenger / metabolism*
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcription, Genetic*
beta-Thalassemia / metabolism

Substances

CHTOP protein, human
Nuclear Proteins
RNA, Messenger
Repressor Proteins
Transcription Factors
Arginine
PRMT1 protein, human
PRMT5 protein, human
Protein-Arginine N-Methyltransferases

Grants and funding

This work was supported by the Japan Science and Technology Agency (JP) (JPMJCR13M2) This work was funded by a grant for Core Research for Evolutionary Science and Technology (CREST) from Japan Science and Technology Agency (JPMJCR13M2), a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, & Technology of Japan (MEXT), and JSPS KAKENHI Grant Number 16K18489. Funding for open access charge: Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency.