Using a hydrogen-bond index to predict the gene-silencing efficiency of siRNA based on the local structure of mRNA

TL;DR

This study introduces the hydrogen-bond index as a predictive measure of siRNA gene-silencing efficiency, linking local mRNA structure to silencing effectiveness and aiding future siRNA design.

Contribution

The paper proposes a novel hydrogen-bond index to quantify mRNA local structure and demonstrates its correlation with siRNA silencing efficiency.

Findings

Gene-silencing effect inversely correlates with the H-b index.

Local mRNA structure significantly influences siRNA effectiveness.

H-b index can guide siRNA design for improved gene silencing.

Abstract

The gene silencing effect of short interfering RNA (siRNA) is known to vary strongly with the targeted position of the mRNA. A number of hypotheses have been suggested to explain this phenomenon. We would like to test if this positional effect is mainly due to the secondary structure of the mRNA at the target site. We proposed that this structural factor can be characterized by a single parameter called "the hydrogen bond (H-b) index", which represents the average number of hydrogen bonds formed between nucleotides in the target region and the rest of the mRNA. This index can be determined using a computational approach. We tested the correlation between the H-b index and the gene-silencing effects on three genes (Bcl-2, hTF and cyclin B1) using a variety of siRNAs. We found that the gene-silencing effect is inversely dependent on the H-b index, indicating that the local mRNA structure at the targeted site is the main cause of the positional effect. Based on this finding, we suggest that the H-b index can be a useful guideline for future siRNA design.