Distance constraints between microRNA target sites dictate efficacy and cooperativity

被引：272
作者：
Saetrom, Pal
Heale, Bret S. E.
Snove, Ola, Jr.
Aagaard, Lars
Alluin, Jessica
Rossi, John J. [1 ]
机构：
[1] City Hope Natl Med Ctr, Beckman Res Inst, Div Mol Biol, Duarte, CA 91010 USA
[2] Interagon AS, Laboratoriesenteret, NO-7489 Trondheim, Norway
[3] Norwegian Univ Sci & Technol, Dept Comp & Informat Sci, NO-7491 Trondheim, Norway
[4] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NO-7489 Trondheim, Norway
来源：
NUCLEIC ACIDS RESEARCH | 2007年 / 35卷 / 07期
关键词：
D O I：
10.1093/nar/gkm133
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：
MicroRNAs (miRNAs) have the potential to regulate the expression of thousands of genes, but the mechanisms that determine whether a gene is targeted or not are poorly understood. We studied the genomic distribution of distances between pairs of identical miRNA seeds and found a propensity for moderate distances greater than about 13 nt between seed starts. Experimental data show that optimal down-regulation is obtained when two seed sites are separated by between 13 and 35 nt. By analyzing the distance between seed sites of endogenous miRNAs and transfected small interfering RNAs (siRNAs), we also find that cooperative targeting of sites with a separation in the optimal range can explain some of the siRNA off-target effects that have been reported in the literature.
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收藏
页码：2333 / 2342
页数：10
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