The BCL-2 5′ Untranslated Region Contains an RNA G-Quadruplex-Forming Motif That Modulates Protein Expression

被引：122

作者：

Shahid, Ramla ^{[1
]}

Bugaut, Anthony ^{[1
]}

Balasubramanian, Shankar ^{[1
,2
,3
]}

机构：

[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

[2] Univ Cambridge, Sch Clin Med, Cambridge CB2 0SP, England

[3] Li Ka Shing Ctr, Cambridge Res Inst, Cambridge CB2 0RE, England

来源：

BIOCHEMISTRY | 2010年 / 49卷 / 38期

基金：

英国生物技术与生命科学研究理事会;

关键词：

INTERNAL RIBOSOME ENTRY; MESSENGER-RNA; PROMOTER REGION; TRANSLATION INITIATION; FOLLICULAR LYMPHOMA; NRAS PROTOONCOGENE; EUKARYOTIC CELLS; GENE-EXPRESSION; CANCER-THERAPY; IN-VIVO;

D O I：

10.1021/bi100957h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The BCL-2 gene encodes a 25 kDa membrane protein that plays critical roles in the control of apoptosis. The regulation of BCL-2 gene expression is highly complex and occurs both transcriptionally and posttranscriptionally. In particular, the 5' upstream region of BCL-2 contains a number of elements that control its expression. We have identified a highly conserved 25-nucleotide G-rich sequence (BCL2Q), with potential to fold into a RNA G-quadruplex structure, located 42 nucleotides upstream of the translation start site of human BCL-2. In this study, we used a series of biophysical experiments to show that the BCL2Q sequence folds into a stable RNA G-quadruplex in vitro, and we conducted functional luciferase reporter-based assays, in a cell-free lysate and in three types of human cell lines, to demonstrate that the BCL2Q sequence modulates protein expression in the context of the 493-nucleotide native 5' untranslated region of BCL-2.

引用

页码：8300 / 8306

页数：7

共 57 条

[11]

CHLEQDESCHAMPS CM, 1993, BLOOD, V81, P293

[12] CLONING AND STRUCTURAL-ANALYSIS OF CDNAS FOR BCL-2 AND A HYBRID BCL-2/IMMUNOGLOBULIN TRANSCRIPT RESULTING FROM THE T(14-18) TRANSLOCATION [J].

CLEARY, ML ;

SMITH, SD ;

SKLAR, J .

CELL, 1986, 47 (01) :19-28

[13] NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region [J].

Dai, Jixun ;

Chen, Ding ;

Jones, Roger A. ;

Hurley, Laurence H. ;

Yang, Danzhou .

NUCLEIC ACIDS RESEARCH, 2006, 34 (18) :5133-5144

[14] An intramolecular G-quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution [J].

Dai, JX ;

Dexheimer, TS ;

Chen, D ;

Carver, M ;

Ambrus, A ;

Jones, RA ;

Yang, DZ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (04) :1096-1098

[15]

DESOIZE B, 1994, ANTICANCER RES, V14, P2291

[16] Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter [J].

Dexheimer, TS ;

Sun, D ;

Hurley, LH .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (16) :5404-5415

[17] Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides [J].

Dias, N ;

Stein, CA .

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2002, 54 (03) :263-269

[18] UTILITY OF FIREFLY LUCIFERASE AS A REPORTER GENE FOR PROMOTER ACTIVITY IN TRANSGENIC MICE [J].

DILELLA, AG ;

HOPE, DA ;

CHEN, H ;

TRUMBAUER, M ;

SCHWARTZ, RJ ;

SMITH, RG .

NUCLEIC ACIDS RESEARCH, 1988, 16 (09) :4159-4159

[19] The immunoglobulin heavy-chain gene 3′ enhancers deregulate bcl-2 promoter usage in t(14;18) lymphoma cells [J].

Duan, H. ;

Heckman, C. A. ;

Boxer, L. M. .

ONCOGENE, 2007, 26 (18) :2635-2641

[20] ISOLATION AND CHARACTERIZATION OF THE CHICKEN BCL-2 GENE - EXPRESSION IN A VARIETY OF TISSUES INCLUDING LYMPHOID AND NEURONAL ORGANS IN ADULT AND EMBRYO [J].

EGUCHI, Y ;

EWERT, DL ;

TSUJIMOTO, Y .

NUCLEIC ACIDS RESEARCH, 1992, 20 (16) :4187-4192

← 1 2 3 4 5 6 →