Growth-restricting effects of siRNA transfections: a largely deterministic combination of off-target binding and hybridization-independent competition Article Swipe
N. Daga
,
Simone Eicher
,
Abhilash Kannan
,
Alain Casanova
,
Shyan Huey Low
,
Saskia Kreibich
,
Daniel Andritschke
,
Mario Emmenlauer
,
Jeremy L. Jenkins
,
Wolf‐Dietrich Hardt
,
Urs F. Greber
,
Christoph Dehio
,
Christian von Mering
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gky798
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1093/nar/gky798
Perturbation of gene expression by means of synthetic small interfering RNAs (siRNAs) is a powerful way to uncover gene function. However, siRNA technology suffers from sequence-specific off-target effects and from limitations in knock-down efficiency. In this study, we assess a further problem: unintended effects of siRNA transfections on cellular fitness/proliferation. We show that the nucleotide compositions of siRNAs at specific positions have reproducible growth-restricting effects on mammalian cells in culture. This is likely distinct from hybridization-dependent off-target effects, since each nucleotide residue is seen to be acting independently and additively. The effect is robust and reproducible across different siRNA libraries and also across various cell lines, including human and mouse cells. Analyzing the growth inhibition patterns in correlation to the nucleotide sequence of the siRNAs allowed us to build a predictor that can estimate growth-restricting effects for any arbitrary siRNA sequence. Competition experiments with co-transfected siRNAs further suggest that the growth-restricting effects might be linked to an oversaturation of the cellular miRNA machinery, thus disrupting endogenous miRNA functions at large. We caution that competition between siRNA molecules could complicate the interpretation of double-knockdown or epistasis experiments, and potential interactions with endogenous miRNAs can be a factor when assaying cell growth or viability phenotypes.
Related Topics
Concepts
Biology
Small interfering RNA
Gene knockdown
Gene silencing
microRNA
Transfection
Trans-acting siRNA
Gene expression
RNA interference
Gene
Cell biology
Genetics
RNA
Computational biology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/nar/gky798
- https://academic.oup.com/nar/article-pdf/46/18/9309/26001278/gky798.pdf
- OA Status
- gold
- Cited By
- 11
- References
- 43
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2896430964
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2896430964Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/nar/gky798Digital Object Identifier
- Title
-
Growth-restricting effects of siRNA transfections: a largely deterministic combination of off-target binding and hybridization-independent competitionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-09-11Full publication date if available
- Authors
-
N. Daga, Simone Eicher, Abhilash Kannan, Alain Casanova, Shyan Huey Low, Saskia Kreibich, Daniel Andritschke, Mario Emmenlauer, Jeremy L. Jenkins, Wolf‐Dietrich Hardt, Urs F. Greber, Christoph Dehio, Christian von MeringList of authors in order
- Landing page
-
https://doi.org/10.1093/nar/gky798Publisher landing page
- PDF URL
-
https://academic.oup.com/nar/article-pdf/46/18/9309/26001278/gky798.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://academic.oup.com/nar/article-pdf/46/18/9309/26001278/gky798.pdfDirect OA link when available
- Concepts
-
Biology, Small interfering RNA, Gene knockdown, Gene silencing, microRNA, Transfection, Trans-acting siRNA, Gene expression, RNA interference, Gene, Cell biology, Genetics, RNA, Computational biologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
11Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2024: 2, 2023: 1, 2021: 2, 2020: 2Per-year citation counts (last 5 years)
- References (count)
-
43Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.us | 126 |
| abstract_inverted_index.we | 37 |
| abstract_inverted_index.The | 90 |
| abstract_inverted_index.and | 28, 88, 94, 100, 108, 186 |
| abstract_inverted_index.any | 137 |
| abstract_inverted_index.can | 132, 192 |
| abstract_inverted_index.for | 136 |
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