SiAbasic: A comprehensive database for potent siRNA-6Ø sequences without off-target effects

Jongyeun Park, Seung Hyun Ahn, Kwang Moon Cho, Dowoon Gu, Eun Sook Jang, Sung Wook Chi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2-6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80-100%), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA-target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2-5) in siRNA-6Ø required the range of stability for effective on-target activity (-6 ≤ δG[2:5] ≤ -3.5 kcal mol -1). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named 'siAbasic' that provided the list of potent siRNA-6Ø sequences for most of human and mouse genes (≥ ∼95%), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6Ø sequences without concerning off-target effects for experimental and clinical purposes.

Original languageEnglish
JournalDatabase
Volume2018
Issue number2018
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

small interfering RNA
RNA
Small Interfering RNA
Databases
MicroRNAs
microRNA
Nucleotides
Nucleation
Cytosine Nucleotides
nucleotides
Conserved Sequence
cytosine
guanine
Base Composition
Guanine
Bioinformatics
RNA Interference
Computational Biology
Polymorphism
RNA interference

ASJC Scopus subject areas

  • Information Systems
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

SiAbasic : A comprehensive database for potent siRNA-6Ø sequences without off-target effects. / Park, Jongyeun; Ahn, Seung Hyun; Cho, Kwang Moon; Gu, Dowoon; Jang, Eun Sook; Chi, Sung Wook.

In: Database, Vol. 2018, No. 2018, 01.01.2018.

Research output: Contribution to journalArticle

Park, Jongyeun ; Ahn, Seung Hyun ; Cho, Kwang Moon ; Gu, Dowoon ; Jang, Eun Sook ; Chi, Sung Wook. / SiAbasic : A comprehensive database for potent siRNA-6Ø sequences without off-target effects. In: Database. 2018 ; Vol. 2018, No. 2018.
@article{3a94d1043d2741289e82ff23db8811bb,
title = "SiAbasic: A comprehensive database for potent siRNA-6{\O} sequences without off-target effects",
abstract = "Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6{\O}), of which impaired base pairing destabilizes transitional nucleation (positions 2-6). However, siRNA-6{\O} varied in its conservation of on-target activity (∼80-100{\%}), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA-target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2-5) in siRNA-6{\O} required the range of stability for effective on-target activity (-6 ≤ δG[2:5] ≤ -3.5 kcal mol -1). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named 'siAbasic' that provided the list of potent siRNA-6{\O} sequences for most of human and mouse genes (≥ ∼95{\%}), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6{\O} sequences without concerning off-target effects for experimental and clinical purposes.",
author = "Jongyeun Park and Ahn, {Seung Hyun} and Cho, {Kwang Moon} and Dowoon Gu and Jang, {Eun Sook} and Chi, {Sung Wook}",
year = "2018",
month = "1",
day = "1",
doi = "10.1093/database/bay109",
language = "English",
volume = "2018",
journal = "Database : the journal of biological databases and curation",
issn = "1758-0463",
publisher = "Oxford University Press",
number = "2018",

}

TY - JOUR

T1 - SiAbasic

T2 - A comprehensive database for potent siRNA-6Ø sequences without off-target effects

AU - Park, Jongyeun

AU - Ahn, Seung Hyun

AU - Cho, Kwang Moon

AU - Gu, Dowoon

AU - Jang, Eun Sook

AU - Chi, Sung Wook

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2-6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80-100%), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA-target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2-5) in siRNA-6Ø required the range of stability for effective on-target activity (-6 ≤ δG[2:5] ≤ -3.5 kcal mol -1). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named 'siAbasic' that provided the list of potent siRNA-6Ø sequences for most of human and mouse genes (≥ ∼95%), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6Ø sequences without concerning off-target effects for experimental and clinical purposes.

AB - Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2-6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80-100%), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA-target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2-5) in siRNA-6Ø required the range of stability for effective on-target activity (-6 ≤ δG[2:5] ≤ -3.5 kcal mol -1). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named 'siAbasic' that provided the list of potent siRNA-6Ø sequences for most of human and mouse genes (≥ ∼95%), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6Ø sequences without concerning off-target effects for experimental and clinical purposes.

UR - http://www.scopus.com/inward/record.url?scp=85055076978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055076978&partnerID=8YFLogxK

U2 - 10.1093/database/bay109

DO - 10.1093/database/bay109

M3 - Article

C2 - 30321353

AN - SCOPUS:85055076978

VL - 2018

JO - Database : the journal of biological databases and curation

JF - Database : the journal of biological databases and curation

SN - 1758-0463

IS - 2018

ER -