Intron-mediated enhancement

Intron-mediated enhancement (IME) is the ability of an intron sequence to enhance the expression of a gene containing that intron. In particular, the intron must be present in the transcribed region of the gene for enhancement to occur, differentiating IME from the action of typical transcriptional enhancers.[1] Descriptions of this phenomenon were first published in cultured maize cells in 1987,[2] and the term "intron-mediated enhancement" was subsequently coined in 1990.[3] A number of publications have demonstrated that this phenomenon is conserved across eukaryotes, including humans,[4] mice,[5] Arabidopsis,[6] rice,[7][8] and C. elegans.[9] However, the mechanism(s) by which IME works are still not completely understood.[10]

When testing to see whether any given intron enhances the expression of a gene, it is typical to compare the expression of two constructs, one containing the intron and one without it, and to express the difference between the two results as a "fold increase" in enhancement. Further experiments can specifically point to IME as the cause of expression enhancement - one of the most common is to move the intron upstream of the transcription start site, removing it from the transcript. If the intron can no longer enhance expression, then inclusion of the intron in the transcript is important, and the intron probably causes IME.

Not all introns enhance gene expression, but those that do can enhance expression between 2– and >1,000–fold relative to an intronless control.[11] In Arabidopsis and other plant species, the IMEter has been developed to calculate the likelihood that an intron sequence will enhance gene expression.[12] It does this by calculating a score based on the patterns of nucleotide sequences within the target sequence. The position of an intron within the transcript is also important - the closer an intron is to the start (5' end) of a transcript, the greater its enhancement of gene expression.[13]

References

  1. ↑ Rose, A. B. (2008-01-01). "Intron-mediated regulation of gene expression". Current Topics in Microbiology and Immunology. 326: 277–290. ISSN 0070-217X. PMID 18630758.
  2. ↑ Callis, J.; Fromm, M.; Walbot, V. (1987-12-01). "Introns increase gene expression in cultured maize cells". Genes & Development. 1 (10): 1183–1200. doi:10.1101/gad.1.10.1183. ISSN 0890-9369. PMID 2828168.
  3. ↑ Mascarenhas, D; Mettler, IJ; Pierce, DA; Lowe, HW (1990). "Intron-mediated enhancement of heterologous gene expression in maize". Plant Molecular Biology. 15 (6): 913–920. doi:10.1007/BF00039430. PMID 2103480. no
  4. ↑ Jonsson, JJ; Foresman, MD; Wilson, N; McIvor, RS (1990). "Intron requirement for expression of the human purine nucleoside phosphorylase gene". Nucleic Acids Research. 20 (12): 3191–3198. doi:10.1093/nar/20.12.3191. PMC 312458Freely accessible. PMID 1620616.
  5. ↑ Palmiter, RD; Sandgren, EP; Avarbock, MR; Allen, DD; Brinster, RL (1991). "Heterologous introns can enhance expression of transgenes in mice". PNAS. 88 (2): 478–482. doi:10.1073/pnas.88.2.478. PMC 50834Freely accessible. PMID 1988947. no
  6. ↑ Rose, AB; Last, RL (2003). "Introns act post-transcriptionally to increase expression of the Arabidopsis thaliana tryptophan pathway gene PAT1". The Plant Journal. 11 (3): 455–464. doi:10.1046/j.1365-313X.1997.11030455.x. PMID 9107035.
  7. ↑ Jeon, JS; Lee, S; Jung, KH; Jun, SH; Kim, C; An, G (2000). "Tissue-Preferential Expression of a Rice α-Tubulin Gene, OsTubA1, Mediated by the First Intron". Plant Physiology. 123 (3): 1005–1014. doi:10.1104/pp.123.3.1005. PMC 59063Freely accessible. PMID 10889249.
  8. ↑ Morello, L; Bardini, M; Sala, F; Breviario, D (2002). "A long leader intron of the Ostub16 rice β-tubulin gene is required for high-level gene expression and can autonomously promote transcription both in vivo and in vitro". The Plant Journal. 29 (1): 33–44. doi:10.1046/j.0960-7412.2001.01192.x. PMID 12060225.
  9. ↑ Ho, SH; So, GMK; Chow, KL (2001). "Postembryonic expression of Caenorhabditis elegans mab-21 and its requirement in sensory ray differentiation". Developmental Dynamics. 221 (4): 422–430. doi:10.1002/dvdy.1161. PMID 11500979.
  10. ↑ Gallegos, Jenna E.; Rose, Alan B. (2015-08-01). "The enduring mystery of intron-mediated enhancement". Plant Science: An International Journal of Experimental Plant Biology. 237: 8–15. doi:10.1016/j.plantsci.2015.04.017. ISSN 1873-2259. PMID 26089147.
  11. ↑ Rose, A (2002). "Requirements for intron-mediated enhancement of gene expression in Arabidopsis". RNA. 8 (11): 1444–53. doi:10.1017/S1355838202020551. PMC 1370350Freely accessible. PMID 12458797.
  12. ↑ Rose, Alan B.; Elfersi, Tali; Parra, Genis; Korf, Ian (2008-03-01). "Promoter-Proximal Introns in Arabidopsis thaliana Are Enriched in Dispersed Signals that Elevate Gene Expression". The Plant Cell. 20 (3): 543–551. doi:10.1105/tpc.107.057190. ISSN 1532-298X. PMC 2329928Freely accessible. PMID 18319396.
  13. ↑ Rose, Alan B. (2004-12-01). "The effect of intron location on intron-mediated enhancement of gene expression in Arabidopsis". The Plant Journal. 40 (5): 744–751. doi:10.1111/j.1365-313X.2004.02247.x. ISSN 1365-313X.
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