Antisense RNA

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Antisense RNA is single-stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell. Antisense RNA may be introduced into a cell to inhibit translation of a complementary mRNA by base pairing to it and physically obstructing the translation machinery. This effect is therefore stoichiometric. An example of naturally occurring mRNA antisense mechanism is the hok/sok system of the E.coli R1 plasmid. Antisense RNA has long been thought of as a promising technique for disease therapy; the only such case to have reached the market is the drug fomivirsen. One commentator has characterized antisense RNA as one of "dozens of technologies that are gorgeous in concept, but exasperating in [commercialization]".[1] Generally, antisense RNA still lack effective design, biological activity, and efficient route of administration.[2]

Historically, the effects of antisense RNA have often been confused with the effects of RNA interference, a related process in which double-stranded RNA fragments called small interfering RNAs trigger catalytically mediated gene silencing, most typically by targeting the RNA-induced silencing complex (RISC) to bind to and degrade the mRNA. Attempts to genetically engineer transgenic plants to express antisense RNA instead activate the RNAi pathway, although the processes result in differing magnitudes of the same downstream effect, gene silencing. Well-known examples include the Flavr Savr tomato and two cultivars of ringspot-resistant papaya.[3][4]

Transcription of longer cis-antisense transcripts is a common phenomenon in the mammalian transcriptome.[5] Although the function of some cases have been described, such as the Zeb2/Sip1 antisense RNA, no general function has been elucidated. In the case of Zeb2/Sip1,[6] the antisense noncoding RNA is opposite the 5' splice site of an intron in the 5'UTR of the Zeb2 mRNA. Expression of the antisense ncRNA prevents splicing of an intron that contains a ribosome entry site necessary for efficient expression of the Zeb2 protein. Transcription of long antisense ncRNAs is often concordant with the associated protein-coding gene,[7] but more detailed studies have revealed that the relative expression patterns of the mRNA and antisense ncRNA are complex.[8][9]

References

  1. ^ DePalma, Angelo (August 2005), "Twenty-Five Years of Biotech Trends", Genetic Engineering News, vol. 25, no. 14, Mary Ann Liebert, pp. 1, 14–23, ISSN 1935-472X, retrieved 2008-08-17
  2. ^ Antisense Oligonucleotides: Basic Concepts and Mechanisms Nathalie Dias and C. A. Stein. Columbia University, New York, New York 10032
  3. ^ Sanders RA, Hiatt W. (2005). Tomato transgene structure and silencing. Nat Biotechnol 23(3):287-9. PMID 15765076
  4. ^ Chiang C, Wang J, Jan F, Yeh S, Gonsalves D (2001). "Comparative reactions of recombinant papaya ringspot viruses with chimeric coat protein (CP) genes and wild-type viruses on CP-transgenic papaya". J Gen Virol Pt 11): 2827-36. PMID 11602796
  5. ^ Katayama S, Tomaru Y, Kasukawa T; et al. (2005). "Antisense transcription in the mammalian transcriptome". Science (New York, N.Y.). 309 (5740): 1564–6. doi:10.1126/science.1112009. PMID 16141073. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Beltran M, Puig I, Peña C; et al. (2008). "A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition". Genes & development. 22 (6): 756–69. doi:10.1101/gad.455708. PMC 2275429. PMID 18347095. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Engström PG, Suzuki H, Ninomiya N; et al. (2006). "Complex Loci in human and mouse genomes". PLoS genetics. 2 (4): e47. doi:10.1371/journal.pgen.0020047. PMC 1449890. PMID 16683030. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  8. ^ Dinger ME, Amaral PP, Mercer TR; et al. (2008). "Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation". Genome research. 18 (9): 1433–45. doi:10.1101/gr.078378.108. PMID 18562676. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008). "Specific expression of long noncoding RNAs in the mouse brain". Proceedings of the National Academy of Sciences of the United States of America. 105 (2): 716–21. doi:10.1073/pnas.0706729105. PMC 2206602. PMID 18184812. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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