Journal
NUCLEIC ACIDS RESEARCH
Volume 35, Issue 7, Pages 2333-2342Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkm133
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Funding
- NIAID NIH HHS [AI29329, R37 AI029329, R01 AI042552, R01 AI029329, AI42552] Funding Source: Medline
- PHS HHS [HLB 07470] Funding Source: Medline
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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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