Recognition of Chromosomal DNA inside Cells by Locked Nucleic Acids

被引:24
作者
Beane, Randall [1 ,2 ]
Gabillet, Sylvie [3 ]
Montaillier, Christophe [3 ]
Arar, Khalil [3 ]
Corey, David R. [1 ,2 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA
[3] SIGMA Aldrich Genopole Campus 1 5, F-91030 Evry, France
基金
美国国家卫生研究院;
关键词
D O I
10.1021/bi801930p
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
Sequence-selective recognition of DNA inside cells by oligonucleotides would provide valuable insights into cellular processes and new leads for therapeutics. Recent work, however, has shown that noncoding RNA transcripts overlap chromosomal DNA. These RNAs provide alternate targets for oligonucleotides designed to bind promoter DNA, potentially overturning previous assumptions about mechanism. Here, we show that antigene locked nucleic acids (agLNAs) reduce RNA levels of targeted genes, block RNA polymerase and transcription factor association at gene promoters, and bind to chromosomal DNA. These data suggest that the mechanism of LNAs involves recognition of chromosomal DNA and that LNAs are bona fide antigene molecules.
引用
收藏
页码:13147 / 13149
页数:3
相关论文
共 23 条
[1]   Inhibiting gene expression with locked nucleic acids (LNAs) that target chromosomal DNA [J].
Beane, Randall L. ;
Ram, Rosalyn ;
Gabillet, Sylvie ;
Arar, Khalil ;
Monia, Brett P. ;
Corey, David R. .
BIOCHEMISTRY, 2007, 46 (25) :7572-7580
[2]   ANTISENSE AND ANTIGENE PROPERTIES OF PEPTIDE NUCLEIC-ACIDS [J].
HANVEY, JC ;
PEFFER, NJ ;
BISI, JE ;
THOMSON, SA ;
CADILLA, R ;
JOSEY, JA ;
RICCA, DJ ;
HASSMAN, CF ;
BONHAM, MA ;
AU, KG ;
CARTER, SG ;
BRUCKENSTEIN, DA ;
BOYD, AL ;
NOBLE, SA ;
BABISS, LE .
SCIENCE, 1992, 258 (5087) :1481-1485
[3]   Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs [J].
Janowski, BA ;
Huffman, KE ;
Schwartz, JC ;
Ram, R ;
Hardy, D ;
Shames, DS ;
Minna, JD ;
Corey, DR .
NATURE CHEMICAL BIOLOGY, 2005, 1 (04) :216-222
[4]   Inhibiting transcription of chromosomal DNA with antigene peptide nucleic acids [J].
Janowski, BA ;
Kaihatsu, K ;
Huffman, KE ;
Schwartz, JC ;
Ram, R ;
Hardy, D ;
Mendelson, CR ;
Corey, DR .
NATURE CHEMICAL BIOLOGY, 2005, 1 (04) :210-215
[5]   Activating gene expression in mammalian cells with promoter-targeted duplex RNAs [J].
Janowski, Bethany A. ;
Younger, Scott T. ;
Hardy, Daniel B. ;
Ram, Rosalyn ;
Huffman, Kenneth E. ;
Corey, David R. .
NATURE CHEMICAL BIOLOGY, 2007, 3 (03) :166-173
[6]   Involvement of AGO1 and AGO2 in mammalian transcriptional silencing [J].
Janowski, Bethany A. ;
Huffman, Kenneth E. ;
Schwartz, Jacob C. ;
Ram, Rosalyn ;
Nordsell, Robert ;
Shames, David S. ;
Minna, John D. ;
Corey, David R. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (09) :787-792
[7]   Recognition of chromosomal DNA by PNAs [J].
Kaihatsu, K ;
Janowski, BA ;
Corey, DR .
CHEMISTRY & BIOLOGY, 2004, 11 (06) :749-758
[8]   Targeted genome modification via triple helix formation [J].
Kalish, JM ;
Glazer, PM .
THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION, 2005, 1058 :151-161
[9]   2 DISTINCT ESTROGEN-REGULATED PROMOTERS GENERATE TRANSCRIPTS ENCODING THE 2 FUNCTIONALLY DIFFERENT HUMAN PROGESTERONE-RECEPTOR FORM-A AND FORM-B [J].
KASTNER, P ;
KRUST, A ;
TURCOTTE, B ;
STROPP, U ;
TORA, L ;
GRONEMEYER, H ;
CHAMBON, P .
EMBO JOURNAL, 1990, 9 (05) :1603-1614
[10]  
Koch T, 2007, ANTISENSE DRUG TECHN, V2nd ed., P519