Specific residues at every third position of siRNA shape its efficient RNAi activity.

@article{citeulike:1093049, abstract = {Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm ('siExplorer') developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 3-nt periodicity provides a new aspect unveiling siRNA functionality.}, address = {Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.}, author = {Katoh, Takayuki and Suzuki, Tsutomu }, citeulike-article-id = {1093049}, issn = {1362-4962}, journal = {Nucleic Acids Res}, keywords = {sirnarnairnaintereference}, month = {January}, posted-at = {2007-04-26 16:17:59}, priority = {5}, title = {Specific residues at every third position of siRNA shape its efficient RNAi activity.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/17259216}, year = {2007} }

TY - JOUR ID - citeulike:1093049 L3 - citeulike-article-id:1093049 TI - Specific residues at every third position of siRNA shape its efficient RNAi activity. JF - Nucleic Acids Res AD - Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. SN - 1362-4962 N2 - Small interfering RNA (siRNA) induces sequence-specific post-transcriptional gene silencing in mammalian cells. Different efficacy of each siRNA is considered to result from sequence preference by protein components in RNAi. To obtain mechanistic insight into siRNA functionality, here we describe a complete data set of siRNA activities targeting all possible position of a single mRNA in human cells. Seven hundred and two siRNAs covering open reading frame of enhanced green fluorescent protein mRNA ( 720 bases) were examined with minimized error factors. The most important finding is that specific residues at every third position of siRNAs greatly influence its RNAi activity; the optimized base composition at positions 3n + 1 (4,7,10,13,16,19) in siRNAs have positive effects on the activity, which can explain the waving siRNA activity with 3 nucleotides (nt) periodicity in the sequential positions of mRNAs. Since there was an obvious correlation between siRNA activity and its binding affinity to TRBP, a partner protein of human Dicer, the 3-nt periodicity might correlate with the affinity to TRBP. As an algorithm ('siExplorer') developed by this observation successfully calculated the activities of siRNAs targeting endogenous human genes, the 3-nt periodicity provides a new aspect unveiling siRNA functionality. KW - sirnarnairnaintereference AU - Katoh, Takayuki AU - Suzuki, Tsutomu PY - 2007/01/26/ UR - http://view.ncbi.nlm.nih.gov/pubmed/17259216 ER -