Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs
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In this article, the authors used the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) to model differential miRNA proficiencies, thereby improving prediction performance.Abstract:
Most metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23, a mammalian miRNA, also has low proficiency in these cells. Reporter results and array data indicate two properties of these miRNAs that impart low proficiency: their weak predicted seed-pairing stability (SPS) and their high target-site abundance (TA). These two properties also explain differential propensities of small interfering RNAs (siRNAs) to repress unintended targets. Using these insights, we expand the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) to model differential miRNA (and siRNA) proficiencies, thereby improving prediction performance. We propose that siRNAs designed to have both weaker SPS and higher TA will have fewer off-targets without compromised on-target activity.read more
Citations
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
MicroRNAs: Target Recognition and Regulatory Functions
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
Journal ArticleDOI
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