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Small double-stranded RNA (dsRNA) has been found to silence gene expression by an evolutionally conserved mechanism known as [[RNA interference]] or [[RNAi]]. Such dsRNAs are called small interfering RNAs or [[siRNA]]. RNAi can occur at both transcriptional and post-transcriptional levels. Surprisingly, two recent studies have found that dsRNA can also activate gene expression, a mechanism that has been termed "small RNA-induced gene activation" or '''RNAa'''.<ref name="pnas">{{cite journal |author=Li LC, Okino ST, Zhao H, ''et al.'' |title=Small dsRNAs induce transcriptional activation in human cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue=46 |pages=17337–42 |year=2006 |month=November |pmid=17085592 |pmc=1859931 |doi=10.1073/pnas.0607015103 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=17085592}}</ref><ref name="ncb">{{cite journal |author=Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR |title=Activating gene expression in mammalian cells with promoter-targeted duplex RNAs |journal=Nat. Chem. Biol. |volume=3 |issue=3 |pages=166–73 |year=2007 |month=March |pmid=17259978 |doi=10.1038/nchembio86010.1038/nchembio860}}</ref><ref name=LiLC>{{cite book |chapterurl=http://www.horizonpress.com/rnareg|author= Li LC|year=2008|chapter=Small RNA-Mediated Gene Activation|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press |isbn=978-1-904455-25-7}}</ref> It has been shown that dsRNAs targeting gene promoters induce potent transcriptional activation of associated genes. Both studies demonstrate RNAa in human cells using synthetic dsRNAs termed small activating RNAs ([[saRNA]]s). Endogenous miRNA that cause RNAa has also been found in humans.<ref>{{cite journal | author=Check E| title=RNA interference: hitting the on switch| journal=Nature| year=2007| volume=448| issue=7156| pages=855–8| pmid=17713502| doi=10.1038/448855a}}</ref> It is currently unknown if RNAa is conserved in other organisms.
Small double-stranded RNA (dsRNA) has been found to silence gene expression by an evolutionally conserved mechanism known as [[RNA interference]] or [[RNAi]]. Such dsRNAs are called small interfering RNAs or [[siRNA]]. RNAi can occur at both transcriptional and post-transcriptional levels. Surprisingly, two recent studies have found that dsRNA can also activate gene expression, a mechanism that has been termed "small RNA-induced gene activation" or '''RNAa'''.<ref name="pnas">{{cite journal |author=Li LC, Okino ST, Zhao H, ''et al.'' |title=Small dsRNAs induce transcriptional activation in human cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue=46 |pages=17337–42 |year=2006 |month=November |pmid=17085592 |pmc=1859931 |doi=10.1073/pnas.0607015103 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=17085592}}</ref><ref name="ncb">{{cite journal |author=Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR |title=Activating gene expression in mammalian cells with promoter-targeted duplex RNAs |journal=Nat. Chem. Biol. |volume=3 |issue=3 |pages=166–73 |year=2007 |month=March |pmid=17259978 |doi=10.1038/nchembio86010.1038/nchembio860}}</ref><ref name=LiLC>{{cite book |chapterurl=http://www.horizonpress.com/rnareg|author= Li LC|year=2008|chapter=Small RNA-Mediated Gene Activation|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press |isbn=978-1-904455-25-7}}</ref> It has been shown that dsRNAs targeting gene promoters induce potent transcriptional activation of associated genes. Both studies demonstrate RNAa in human cells using synthetic dsRNAs termed small activating RNAs ([[saRNA]]s). Endogenous miRNA that cause RNAa has also been found in humans.<ref>{{cite journal | author=Check E| title=RNA interference: hitting the on switch| journal=Nature| year=2007| volume=448| issue=7156| pages=855–8| pmid=17713502| doi=10.1038/448855a}}</ref> Very recently, RNAa has been demonstrated in several mammalian species other than human including non-human primates, mouse and rat, <ref>{{cite journal | author=Huang V et al.| title=RNAa is conserved in mammalian cells| journal=PLoS One| year=2010| volume=5| issue=1 |pages=e8848| doi=10.1371/journal.pone.0008848 |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008848}}</ref> suggesting that RNAa is is a general gene regulation mechanism conserved at least in mammals. It is likely that RNAa also exists in other organisms.


Another surprising observation is that gene activation by RNAa is long-lasting. Induction of gene expression has been seen to last for over ten days. The prolonged effect of RNAa could be attributed to [[epigenetic]] changes at dsRNA target sites.
Another surprising observation is that gene activation by RNAa is long-lasting. Induction of gene expression has been seen to last for over ten days. The prolonged effect of RNAa could be attributed to [[epigenetic]] changes at dsRNA target sites.

Revision as of 17:49, 23 January 2010

Small double-stranded RNA (dsRNA) has been found to silence gene expression by an evolutionally conserved mechanism known as RNA interference or RNAi. Such dsRNAs are called small interfering RNAs or siRNA. RNAi can occur at both transcriptional and post-transcriptional levels. Surprisingly, two recent studies have found that dsRNA can also activate gene expression, a mechanism that has been termed "small RNA-induced gene activation" or RNAa.[1][2][3] It has been shown that dsRNAs targeting gene promoters induce potent transcriptional activation of associated genes. Both studies demonstrate RNAa in human cells using synthetic dsRNAs termed small activating RNAs (saRNAs). Endogenous miRNA that cause RNAa has also been found in humans.[4] Very recently, RNAa has been demonstrated in several mammalian species other than human including non-human primates, mouse and rat, [5] suggesting that RNAa is is a general gene regulation mechanism conserved at least in mammals. It is likely that RNAa also exists in other organisms.

Another surprising observation is that gene activation by RNAa is long-lasting. Induction of gene expression has been seen to last for over ten days. The prolonged effect of RNAa could be attributed to epigenetic changes at dsRNA target sites.

References

  1. ^ Li LC, Okino ST, Zhao H; et al. (2006). "Small dsRNAs induce transcriptional activation in human cells". Proc. Natl. Acad. Sci. U.S.A. 103 (46): 17337–42. doi:10.1073/pnas.0607015103. PMC 1859931. PMID 17085592. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR (2007). "Activating gene expression in mammalian cells with promoter-targeted duplex RNAs". Nat. Chem. Biol. 3 (3): 166–73. doi:10.1038/nchembio86010.1038/nchembio860. PMID 17259978. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Li LC (2008). "Small RNA-Mediated Gene Activation". RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press. ISBN 978-1-904455-25-7. {{cite book}}: External link in |chapterurl= (help); Unknown parameter |chapterurl= ignored (|chapter-url= suggested) (help)
  4. ^ Check E (2007). "RNA interference: hitting the on switch". Nature. 448 (7156): 855–8. doi:10.1038/448855a. PMID 17713502.
  5. ^ Huang V; et al. (2010). "RNAa is conserved in mammalian cells". PLoS One. 5 (1): e8848. doi:10.1371/journal.pone.0008848. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: unflagged free DOI (link)

Further reading

External links

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