The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Small dsRNAs induce transcriptional activation in human cells
Open accessAbstract
Recent studies have shown that small noncoding RNAs, such as microRNAs and siRNAs, regulate gene expression at multiple levels including chromatin architecture, transcription, RNA editing, RNA stability, and translation. Each form of RNA-dependent regulation has been generally found to silence homologous sequences and collectively called RNAi. To further study the regulatory role of small RNAs at the transcriptional level, we designed and synthesized 21-nt dsRNAs targeting selected promoter regions of human genes E-cadherin, p21 WAF1/CIP1 (p21), and VEGF. Surprisingly, transfection of these dsRNAs into human cell lines caused long-lasting and sequence-specific induction of targeted genes. dsRNA mutation studies reveal that the 5′ end of the antisense strand, or “seed” sequence, is critical for activity. Mechanistically, the dsRNA-induced gene activation requires the Argonaute 2 (Ago2) protein and is associated with a loss of lysine-9 methylation on histone 3 at dsRNA-target sites. In conclusion, we have identified several dsRNAs that activate gene expression by targeting noncoding regulatory regions in gene promoters. These findings reveal a more diverse role for small RNA molecules in the regulation of gene expression than previously recognized and identify a potential therapeutic use for dsRNA in targeted gene activation.
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Cites
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The current state and future directions of RNAi-based therapeutics
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Diversifying microRNA sequence and function
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Genetic compensation triggered by mutant mRNA degradation
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Genetic compensation: A phenomenon in search of mechanisms
El-Brolosy, M. A., & Stainier, D. Y. R. (2017) · PLOS Genetics · doi:10.1371/journal.pgen.1006780 · Cited by 829
Non-coding RNAs as regulators of gene expression and epigenetics
Kaikkonen, M. U., Lam, M. T. Y., & Glass, C. K. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr097 · Cited by 764
Metadata
- Authors
- Li, L.-C., Okino, S. T., Zhao, H., Pookot, D., Place, R. F., Urakami, S., Enokida, H., & Dahiya, R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-11-14
- Volume
- 103
- Issue
- 46
- Pages
- 17337-17342
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2105444747
- Cited by
- 769
- References
- 36
- FWCI
- 14.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Li, L.-C., Okino, S. T., Zhao, H., Pookot, D., Place, R. F., Urakami, S., Enokida, H., & Dahiya, R. (2006). Small dsRNAs induce transcriptional activation in human cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0607015103
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