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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Trans-Splicing


High impact information on Trans-Splicing

  • We suggest from these experiments that the product of the tscA gene may be a small chloroplast RNA that acts in trans in the first trans-splicing reaction of psaA [6].
  • RNA editing in intron sequences may thus be required for the trans-splicing reaction [7].
  • Degradation of U2, U4, or U6 snRNA by site-directed cleavage with complementary deoxyoligonucleotides and RNAase H inhibits trans splicing of the spliced leader (SL) RNA and newly synthesized alpha-tubulin pre-mRNAs [8].
  • Mutant phenotypes support a trans-splicing mechanism for the expression of the tripartite psaA gene in the C. reinhardtii chloroplast [9].
  • The evidence suggests that the actin mRNA leader sequence is acquired from this novel nucleotide transcript by an intermolecular trans-splicing mechanism [10].

Chemical compound and disease context of Trans-Splicing


Biological context of Trans-Splicing

  • Although a multitude of reactions can be enhanced by this class of catalyst, including trans-splicing activity of the group I intron (which could be applied to gene correction), RNA-cleaving RNA enzymes or "ribozymes" hold center stage because of their tremendous potential for mediating gene inactivation [12].
  • We show here that lola mRNAs are generated by alternative trans-splicing of exons sequentially encoded by the same DNA strand [13].
  • Here, we investigate the mechanisms of Sp1 pre-mRNA trans-splicing with human cells expressing modified Sp1 transgenes [14].
  • Highlights include the demonstration that exonic enhancers can promote trans splicing and that an excess of the serine and arginine rich family of splicing proteins can obviate the requirement for U1 small nuclear ribonucleoprotein particle in splicing [15].
  • These non-polyadenylated branched Y-shaped RNA molecules are analogous to the lariat shaped introns of higher eukaryotes and presumably represent the released intron-like by-products of a trans-splicing reaction which joins the mini-exon and the major coding-exon [16].

Anatomical context of Trans-Splicing


Associations of Trans-Splicing with chemical compounds

  • This trans-splicing reaction has ATP, Mg(2+), and splice-site sequence requirements similar to those of cis-splicing reactions [22].
  • These features include the glycosomal functions and protein import, the trans-splicing of mRNAs, the machineries for controlled protein degradations, the polyamine metabolism, the trypanothione metabolism, the purine salvage enzymes, and the glycolipid anchor for the surface glycoproteins [23].
  • Block substitutions identified the pyrimidine-rich sequences at the alpha-tubulin 3'-splice-acceptor site as a major determinant for accurate trans-splicing downstream and 3'-end formation upstream [24].
  • Natural trans-splicing in carnitine octanoyltransferase pre-mRNAs in rat liver [25].
  • Here we show that exposure of permeable trypanosome cells to S-adenosyl-L-homocysteine inhibits methylation of the nucleosides adjacent to 7-methylguanosine of newly synthesized SL RNA and prevents utilization of the SL RNA in trans splicing [26].

Gene context of Trans-Splicing


Analytical, diagnostic and therapeutic context of Trans-Splicing

  • Western blot analysis of cell extracts from these plants showed a full-length EPSPS, demonstrating that the EPSPSn-In gene product migrated to the chloroplast and underwent trans-splicing [31].
  • Genomic PCR was then used to demonstrate that the 80 kDa ER mRNA was not derived from the trans-splicing of two ER mRNAs but was the result of a genomic rearrangement in which exons 6 and 7 were duplicated in an in-frame fashion [32].
  • Unlike conventional gene therapy, in which exogenous cDNAs are introduced into cells, RNA repair approaches, which are based on spliceosome-mediated pre-mRNA trans-splicing, trans-splicing ribozymes, and tRNA-splicing endonuclease, allow the correction of endogenous RNA species [33].
  • Expression of this gene was demonstrated by Northern blot analysis and its trans-splicing acceptor site was identified by Polymerase Chain Reaction-mediated amplification of its cDNA [34].


  1. Trans-splicing repair of CD40 ligand deficiency results in naturally regulated correction of a mouse model of hyper-IgM X-linked immunodeficiency. Tahara, M., Pergolizzi, R.G., Kobayashi, H., Krause, A., Luettich, K., Lesser, M.L., Crystal, R.G. Nat. Med. (2004) [Pubmed]
  2. Functional repair of a mutant chloride channel using a trans-splicing ribozyme. Rogers, C.S., Vanoye, C.G., Sullenger, B.A., George, A.L. J. Clin. Invest. (2002) [Pubmed]
  3. Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing. Liu, X., Jiang, Q., Mansfield, S.G., Puttaraju, M., Zhang, Y., Zhou, W., Cohn, J.A., Garcia-Blanco, M.A., Mitchell, L.G., Engelhardt, J.F. Nat. Biotechnol. (2002) [Pubmed]
  4. Zinc inhibition of protein trans-splicing and identification of regions essential for splicing and association of a split intein*. Ghosh, I., Sun, L., Xu, M.Q. J. Biol. Chem. (2001) [Pubmed]
  5. Trans-splicing ribozymes for targeted gene delivery. Köhler, U., Ayre, B.G., Goodman, H.M., Haseloff, J. J. Mol. Biol. (1999) [Pubmed]
  6. A small chloroplast RNA may be required for trans-splicing in Chlamydomonas reinhardtii. Goldschmidt-Clermont, M., Choquet, Y., Girard-Bascou, J., Michel, F., Schirmer-Rahire, M., Rochaix, J.D. Cell (1991) [Pubmed]
  7. Trans splicing in Oenothera mitochondria: nad1 mRNAs are edited in exon and trans-splicing group II intron sequences. Wissinger, B., Schuster, W., Brennicke, A. Cell (1991) [Pubmed]
  8. Destruction of U2, U4, or U6 small nuclear RNA blocks trans splicing in trypanosome cells. Tschudi, C., Ullu, E. Cell (1990) [Pubmed]
  9. Mutant phenotypes support a trans-splicing mechanism for the expression of the tripartite psaA gene in the C. reinhardtii chloroplast. Choquet, Y., Goldschmidt-Clermont, M., Girard-Bascou, J., Kück, U., Bennoun, P., Rochaix, J.D. Cell (1988) [Pubmed]
  10. A trans-spliced leader sequence on actin mRNA in C. elegans. Krause, M., Hirsh, D. Cell (1987) [Pubmed]
  11. Intein-mediated cyclization of a soluble and a membrane protein in vivo: function and stability. Siebold, C., Erni, B. Biophys. Chem. (2002) [Pubmed]
  12. Catalytic nucleic acids: from lab to applications. Sun, L.Q., Cairns, M.J., Saravolac, E.G., Baker, A., Gerlach, W.L. Pharmacol. Rev. (2000) [Pubmed]
  13. Alternative trans-splicing of constant and variable exons of a Drosophila axon guidance gene, lola. Horiuchi, T., Giniger, E., Aigaki, T. Genes Dev. (2003) [Pubmed]
  14. Delay in synthesis of the 3' splice site promotes trans-splicing of the preceding 5' splice site. Takahara, T., Tasic, B., Maniatis, T., Akanuma, H., Yanagisawa, S. Mol. Cell (2005) [Pubmed]
  15. Initial splice-site recognition and pairing during pre-mRNA splicing. Reed, R. Curr. Opin. Genet. Dev. (1996) [Pubmed]
  16. Physical identification of branched intron side-products of splicing in Trypanosoma brucei. Ralph, D., Huang, J., Van der Ploeg, L.H. EMBO J. (1988) [Pubmed]
  17. Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors. Lan, N., Howrey, R.P., Lee, S.W., Smith, C.A., Sullenger, B.A. Science (1998) [Pubmed]
  18. Trans splicing integrates an exon of 22 nucleotides into the nad5 mRNA in higher plant mitochondria. Knoop, V., Schuster, W., Wissinger, B., Brennicke, A. EMBO J. (1991) [Pubmed]
  19. Antigenic variation in trypanosomes: secrets surface slowly. Cross, G.A. Bioessays (1996) [Pubmed]
  20. Spliceosome-mediated RNA trans-splicing with recombinant adeno-associated virus partially restores cystic fibrosis transmembrane conductance regulator function to polarized human cystic fibrosis airway epithelial cells. Liu, X., Luo, M., Zhang, L.N., Yan, Z., Zak, R., Ding, W., Mansfield, S.G., Mitchell, L.G., Engelhardt, J.F. Hum. Gene Ther. (2005) [Pubmed]
  21. Diversity of the repertoire of p58 killer cell inhibitory receptors in a single individual. Chwae, Y.J., Cho, S.E., Kim, S.J., Kim, J. Immunol. Lett. (1999) [Pubmed]
  22. Characterization of U4 and U6 interactions with the 5' splice site using a S. cerevisiae in vitro trans-splicing system. Johnson, T.L., Abelson, J. Genes Dev. (2001) [Pubmed]
  23. Molecular mechanisms and therapeutic approaches to the treatment of African trypanosomiasis. Wang, C.C. Annu. Rev. Pharmacol. Toxicol. (1995) [Pubmed]
  24. A common pyrimidine-rich motif governs trans-splicing and polyadenylation of tubulin polycistronic pre-mRNA in trypanosomes. Matthews, K.R., Tschudi, C., Ullu, E. Genes Dev. (1994) [Pubmed]
  25. Natural trans-splicing in carnitine octanoyltransferase pre-mRNAs in rat liver. Caudevilla, C., Serra, D., Miliar, A., Codony, C., Asins, G., Bach, M., Hegardt, F.G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  26. Trans splicing in trypanosomes requires methylation of the 5' end of the spliced leader RNA. Ullu, E., Tschudi, C. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  27. Evidence for in vivo trans splicing of pre-mRNAs in tobacco chloroplasts. Koller, B., Fromm, H., Galun, E., Edelman, M. Cell (1987) [Pubmed]
  28. apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Daigle, I., Li, C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  29. Alternative mRNAs arising from trans-splicing code for mitochondrial and cytosolic variants of Echinococcus granulosus thioredoxin Glutathione reductase. Agorio, A., Chalar, C., Cardozo, S., Salinas, G. J. Biol. Chem. (2003) [Pubmed]
  30. Interplay between AAUAAA and the trans-splice site in processing of a Caenorhabditis elegans operon pre-mRNA. Liu, Y., Huang, T., MacMorris, M., Blumenthal, T. RNA (2001) [Pubmed]
  31. Protein trans-splicing in transgenic plant chloroplast: reconstruction of herbicide resistance from split genes. Chin, H.G., Kim, G.D., Marin, I., Mersha, F., Evans, T.C., Chen, L., Xu, M.Q., Pradhan, S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  32. A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. Pink, J.J., Wu, S.Q., Wolf, D.M., Bilimoria, M.M., Jordan, V.C. Nucleic Acids Res. (1996) [Pubmed]
  33. Spliceosome-mediated RNA trans-splicing. Yang, Y., Walsh, C.E. Mol. Ther. (2005) [Pubmed]
  34. A putative pyruvate dehydrogenase alpha subunit gene from Trypanosoma cruzi. Buscaglia, C.A., Pollevick, G.D., Veloso, C., Lorca, M., Frasch, A.C., Sánchez, D.O. Biochim. Biophys. Acta (1996) [Pubmed]
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