Enhanced mRNA cap methylation increases Cyclin D1 expression and promotes cell transformation

被引：52

作者：

Cowling, V. H. ^{[1
]}

机构：

[1] Univ Dundee, Coll Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland

来源：

ONCOGENE | 2010年 / 29卷 / 06期

关键词：

Cyclin D1; cell transformation; mRNA cap methylation; mRNA translation; C-MYC; CANCER; METHYLTRANSFERASE; TRANSLATION; RECRUITMENT; REPRESSION; APOPTOSIS; BINDING; EIF4E; GENE;

D O I：

10.1038/onc.2009.368

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cap-dependent mRNA translation requires the methylation of the mRNA guanosine cap by RNA guanine-7-methyltransferase (RNMT). mRNA cap methylation was recently described to be rate-limiting for a subset of mRNAs, and to be enhanced by expression of c-Myc and E2F1, although the biological significance of this finding was not investigated. Here, it is reported that increased RNMT expression enhances cellular mRNA cap methyltransferase activity, promotes mammary epithelial cell transformation and cooperates with H-RasV12 or c-Myc to promote fibroblast cell transformation. Cyclin D1 is a prominent oncogene in epithelial tumours. A signi. cant fraction of Cyclin D1 mRNA was found to be unmethylated on the mRNA cap and thus dormant in mammary epithelial cells. Cyclin D1 expression was increased by enhanced mRNA cap methylation. In summary, this report shows that mRNA cap methylation is rate-limiting for expression of an oncogene and cell transformation. Oncogene (2010) 29, 930-936; doi:10.1038/onc.2009.368; published online 16 November 2009

引用

页码：930 / 936

页数：7

共 26 条

[1]

Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors [J].

Bentley, DL .

CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (03) :251-256

[2]

Apoptosis and autophagy induction in mammalian cells by small interfering RNA knockdown of mRNA capping enzymes [J].

Chu, Chun ;

Shatkin, Aaron J. .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (19) :5829-5836

[3]

Specific regulation of mRNA cap methylation by the c-Myc and E2F1 transcription factors [J].

Cole, M. D. ;

Cowling, V. H. .

ONCOGENE, 2009, 28 (09) :1169-1175

[4]

Transcription-independent functions of MYC: regulation of translation and DNA replication [J].

Cole, Michael D. ;

Cowling, Victoria H. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (10) :810-815

[5]

The Myc transactivation domain promotes global phosphorylation of the RNA polymerase II carboxy-terminal domain independently of direct DNA binding [J].

Cowling, Victoria H. ;

Cole, Michael D. .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (06) :2059-2073

[6]

c-Myc transforms human mammary epithelial cells through repression of the Wnt inhibitors DKK1 and SFRP1 [J].

Cowling, Victoria H. ;

D'Cruz, Celina M. ;

Chodosh, Lewis A. ;

Cole, Michael D. .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (14) :5135-5146

[7]

A conserved Myc protein domain, MBIV, regulates DNA binding, apoptosis, transformation, an G2 arrest [J].

Cowling, Victoria H. ;

Chandriani, Sanjay ;

Whitfield, Michael L. ;

Cole, Michael D. .

MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (11) :4226-4239

[8]

DiRenzo J, 2002, CANCER RES, V62, P89

[9]

Viral and cellular mRNA capping: Past and prospects [J].

Furuichi, Y ;

Shatkin, AJ .

ADVANCES IN VIRUS RESEARCH, VOL 55, 2000, 55 :135-184

[10]

eIF4 initiation factors: Effectors of mRNA recruitment to ribosomes and regulators of translation [J].

Gingras, AC ;

Raught, B ;

Sonenberg, N .

ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :913-963

← 1 2 3 →