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PMID: 17259216 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nucleic acids research ·Vol. 35 ·No. 4 ·2007-00-00 ·Pages e27

Katoh T, Suzuki T

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.

MeSH Terms
Algorithms Base Composition Green Fluorescent Proteins/genetics HeLa Cells Humans RNA Interference RNA, Messenger/metabolism RNA, Small Interfering/chemistry RNA-Binding Proteins/metabolism Spectrometry, Fluorescence Thermodynamics
Chemicals
RNA, Messenger RNA, Small Interfering RNA-Binding Proteins enhanced green fluorescent protein trans-activation responsive RNA-binding protein Green Fluorescent Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Katoh Takayuki
Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Suzuki Tsutomu
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl1120
Published
2007-00-00
Epub
2007-00-26
Pages
e27
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1851635
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkl1120 PMC Full Text View journal details
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