Antisense RNA

Antisense RNA (asRNA) is a single-stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell. Some authors have used the term micRNA (mRNA-interfering complementary RNA) to refer to these RNAs but it is not widely used.[1]

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.[2] 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 first antisense therapeutic to reach the market is the drug fomivirsen, approved in 1998. Mipomersen was approved in the united states in 2013. One commentator has characterized antisense RNA as one of "dozens of technologies that are gorgeous in concept, but exasperating in [commercialization]".[3] Generally, antisense RNA still lack effective design, biological activity, and efficient route of administration.[4]

The effects of antisense RNA are related with the effects of RNA interference (RNAi). The RNAi process, found only in eukaryotes, is initiated by double-stranded RNA fragments, which may be created by the expression of an anti-sense RNA followed by the base-pairing of the anti-sense strand to the target transcript.[5] Double-stranded RNA may be created by other mechanisms (including secondary RNA structure). The double-stranded RNA is cleaved into small fragements by DICER, and then a single strand of the fragment is incorporated into the RNA-induced silencing complex (RISC) so that the RISC may bind to and degrade the complementary mRNA target.[6] Some genetically engineered transgenic plants that express antisense RNA do activate the RNAi pathway.[7] This processes resulted in differing magnitudes of gene silencing induced by the expression of antisense RNA. Well-known examples include the Flavr Savr tomato and two cultivars of ringspot-resistant papaya.[8][9]

Transcription of longer cis-antisense transcripts is a common phenomenon in the mammalian transcriptome.[10] 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,[11] 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,[12] but more detailed studies have revealed that the relative expression patterns of the mRNA and antisense ncRNA are complex.[13][14]

See also

References

  1. ↑ Mizuno, T.; Chou, M. Y.; Inouye, M. (1984). "A unique mechanism regulating gene expression: Translational inhibition by a complementary RNA transcript (micRNA)". Proceedings of the National Academy of Sciences of the United States of America. 81 (7): 1966–1970. doi:10.1073/pnas.81.7.1966. PMC 345417Freely accessible. PMID 6201848.
  2. ↑ Weiss, B; Davidkova, G; Zhou, LW (March 1999). "Antisense RNA gene therapy for studying and modulating biological processes.". Cellular and molecular life sciences : CMLS. 55 (3): 334–58. doi:10.1007/s000180050296. PMID 10228554.
  3. ↑ DePalma, Angelo (August 2005). "Twenty-Five Years of Biotech Trends". Genetic Engineering News. 25 (14). Mary Ann Liebert. pp. 1, 14–23. ISSN 1935-472X. Retrieved 2008-08-17.
  4. ↑ Antisense Oligonucleotides: Basic Concepts and Mechanisms Nathalie Dias and C. A. Stein. Columbia University, New York, New York 10032
  5. ↑ Giordano Ennio; Rendina Rosaria; Peluso Ivana; Furia Maria (2002). "RNAi Triggered by Symmetrically Transcribed Transgenes in Drosophila melanogaster". Genetics. 160 (2): 637–648.
  6. ↑ Wilson Ross C.; Doudna Jennifer A. (2013). "Molecular Mechanisms of RNA Interference". Annual Review of Biophysics. 42 (1): 217–239. doi:10.1146/annurev-biophys-083012-130404. PMID 23654304.
  7. ↑ Krieger Elysia K.; Allen Edwards; Gilbertson Larry A.; Roberts James K.; Hiatt William; Sanders Rick A. (2008). "The Flavr Savr Tomato, an Early Example of RNAi Technology". HortScience. 43 (3): 962–964.
  8. ↑ Sanders RA, Hiatt W (2005). "Tomato transgene structure and silencing". Nat Biotechnol. 23 (3): 287–9. doi:10.1038/nbt0305-287b. PMID 15765076.
  9. ↑ Chiang CH, Wang JJ, Jan FJ, Yeh SD, Gonsalves D (November 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. 82 (Pt 11): 2827–36. PMID 11602796.
  10. ↑ Katayama S, Tomaru Y, Kasukawa T, et al. (September 2005). "Antisense transcription in the mammalian transcriptome". Science. 309 (5740): 1564–6. doi:10.1126/science.1112009. PMID 16141073.
  11. ↑ Beltran M, Puig I, Peña C, et al. (March 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 2275429Freely accessible. PMID 18347095.
  12. ↑ Engström PG, Suzuki H, Ninomiya N, et al. (April 2006). "Complex Loci in human and mouse genomes". PLOS Genetics. 2 (4): e47. doi:10.1371/journal.pgen.0020047. PMC 1449890Freely accessible. PMID 16683030.
  13. ↑ Dinger ME, Amaral PP, Mercer TR, et al. (September 2008). "Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation". Genome Research. 18 (9): 1433–45. doi:10.1101/gr.078378.108. PMC 2527704Freely accessible. PMID 18562676.
  14. ↑ Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (January 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 2206602Freely accessible. PMID 18184812.
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