Computational design of artificial RNA molecules for gene regulation

TY - CHAP

T1 - Computational design of artificial RNA molecules for gene regulation

AU - Laganà, Alessandro

AU - Veneziano, Dario

AU - Russo, Francesco

AU - Pulvirenti, Alfredo

AU - Giugno, Rosalba

AU - Croce, Carlo Maria

AU - Ferro, Alfredo

PY - 2015/1/10

Y1 - 2015/1/10

N2 - RNA interference (RNAi) is a powerful tool for the regulation of gene expression. Small exogenous noncoding RNAs (ncRNAs) such as siRNA and shRNA are the active silencing agents, intended to target and cleave complementary mRNAs in a specific way. They are widely and successfully employed in functional studies, and several ongoing and already completed siRNA-based clinical trials suggest encouraging results in the regulation of overexpressed genes in disease. siRNAs share many aspects of their biogenesis and function with miRNAs, small ncRNA molecules transcribed from endogenous genes which are able to repress the expression of target mRNAs by either inhibiting their translation or promoting their degradation. Although siRNA and artificial miRNA molecules can significantly reduce the expression of overexpressed target genes, cancer and other diseases can also be triggered or sustained by upregulated miRNAs. Thus, in the past recent years, molecular tools for miRNA silencing, such as antagomiRs and miRNA sponges, have been developed. These molecules have shown their efficacy in the derepression of genes downregulated by overexpressed miRNAs. In particular, while a single antagomiR is able to inhibit a single complementary miRNA, an artificial sponge construct usually contains one or more binding sites for one or more miRNAs and functions by competing with the natural targets of these miRNAs. As a consequence, natural miRNA targets are reexpressed at their physiological level. In this chapter we review the most successful methods for the computational design of siRNAs, antagomiRs, and miRNA sponges and describe the most popular tools that implement them.

AB - RNA interference (RNAi) is a powerful tool for the regulation of gene expression. Small exogenous noncoding RNAs (ncRNAs) such as siRNA and shRNA are the active silencing agents, intended to target and cleave complementary mRNAs in a specific way. They are widely and successfully employed in functional studies, and several ongoing and already completed siRNA-based clinical trials suggest encouraging results in the regulation of overexpressed genes in disease. siRNAs share many aspects of their biogenesis and function with miRNAs, small ncRNA molecules transcribed from endogenous genes which are able to repress the expression of target mRNAs by either inhibiting their translation or promoting their degradation. Although siRNA and artificial miRNA molecules can significantly reduce the expression of overexpressed target genes, cancer and other diseases can also be triggered or sustained by upregulated miRNAs. Thus, in the past recent years, molecular tools for miRNA silencing, such as antagomiRs and miRNA sponges, have been developed. These molecules have shown their efficacy in the derepression of genes downregulated by overexpressed miRNAs. In particular, while a single antagomiR is able to inhibit a single complementary miRNA, an artificial sponge construct usually contains one or more binding sites for one or more miRNAs and functions by competing with the natural targets of these miRNAs. As a consequence, natural miRNA targets are reexpressed at their physiological level. In this chapter we review the most successful methods for the computational design of siRNAs, antagomiRs, and miRNA sponges and describe the most popular tools that implement them.

KW - antagomiR

KW - Gene expression

KW - miRNA

KW - RNAi

KW - shRNA

KW - siRNA

KW - Sponge

UR - http://www.scopus.com/inward/record.url?scp=84958626883&partnerID=8YFLogxK

U2 - 10.1007/978-1-4939-2291-8_25

DO - 10.1007/978-1-4939-2291-8_25

M3 - Book chapter

AN - SCOPUS:84958626883

SN - 9781493922901

SP - 393

EP - 412

BT - RNA Bioinformatics

PB - Springer New York LLC

ER -