Trans Splicing

Abstract

Exon sequences are normally tethered through introns, which are then spliced out to generate mRNA. In trans‐splicing, the exons are not linked together, which raises issues concerning how the two splice sites are juxtaposed for splicing to occur.

Keywords: pre‐mRNA; splicing factor; nematode; trypanosome; snRNA/snRNP

Figure 1.

Trans‐ and cis‐splicing pathways. Comparable steps in the two reactions are drawn next to each other for direct comparison. The 5′ exon in the trans‐splicing reaction is contained in the SL RNA.

Figure 2.

Predicted secondary structures of SL RNAs from different organisms. Each contains a 5′ terminal stem loop that includes the SL exon and the 5′ splice site (ss, indicated by an arrow). In the 3′ intronic region of the molecule, each SL RNA contains a binding site for the common Sm proteins. Secondary structures are not drawn to scale, and subtle features such as bulges are not noted.

Figure 3.

Trans‐spliceosome assembly. The RNA containing the 3′ splice site (3′ acceptor) interacts with U2 snRNP, assisted by interactions with SR proteins bound to splicing enhancers (enh) or by interactions with U1 snRNP bound downstream (exon definition). The SL RNP interacts with the U4/U6·U5 tri‐snRNP to form the SL·U4/U6·U5 tetra‐snRNP. In a manner dependent on SR proteins, these initial complexes associate functionally, leading to the first catalytic step of the reaction – generation of the free SL exon and the Y‐branched intermediate. In the second step of the reaction, the trans‐spliced product is formed.

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References

Bruzik JP (1996) Splicing glue: a role for SR proteins in trans splicing? Microbial Pathogenesis 21: 149–155.

Denker JA, Maroney PA, Yu Y‐T, Kanost RA and Nilsen TW (1996) Multiple requirements for nematode spliced leader RNP function in trans‐splicing. RNA 2: 746–755.

Evans D, Perez I, MacMorris M, et al. (2001) A complex containing CstF‐64 and the SL2 snRNP connects mRNA 3′ end formation and trans‐splicing in C. elegans operons. Genes and Development 15: 2562–2571.

Liu X, Jiang Q, Mansfield SG, et al. (2002) Partial correction of endogenous ΔF508 CFTR in human cystic fibrosis airway epithelia by spliceosome‐mediated RNA trans‐splicing. Nature Biotechnology 20: 47–52.

Maquat LE and Carmichael GG (2001) Quality control of mRNA function. Cell 104: 173–176.

Maroney PA, Yu Y‐T, Jankowska M and Nilsen TW (1996) Direct analysis of nematode cis‐ and trans‐spliceosomes: a functional role for U5 snRNA in spliced leader addition trans‐splicing and the identification of novel Sm snRNPs. RNA 2: 735–745.

Mongelard F, Labrador M, Baxter EM, Gerasimova TI and Corces VG (2002) Trans‐splicing as a novel mechanism to explain interallelic complementation in Drosophila. Genetics 160: 1481–1487.

Nilsen TW (1997) Trans‐splicing. In: Krainer AR (ed.) Eukaryotic mRNA Processing, pp. 310–334. Oxford, UK: IRL Press.

Nilsen TW (2001) Evolutionary origin of SL‐addition trans‐splicing: still an enigma. Trends in Genetics 17: 678–680.

Sanford JR and Bruzik JP (1999) SR proteins are required for nematode trans‐splicing in vitro. RNA 5: 918–928.

Further Reading

Blumenthal T and Steward K (1997) RNA processing and gene structure. In: Riddle DL, Blumenthal T, Meyer BJ and Priess JR (eds.) C. elegans, II, pp. 117–146. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Bruzik JP, Van Doren K, Hirsh D and Steitz JA (1988) Trans splicing involves a novel form of small nuclear ribonucleoprotein particles. Nature 335: 559–562.

Evans D and Blumenthal T (2000) Trans splicing of polycistronic Caenorhabditis elegans pre‐mRNAs: analysis of the SL2 RNA. Molecular and Cellular Biology 20: 6659–6667.

Kikumori T, Cote GJ and Gagel RF (2001) Promiscuity of pre‐mRNA spliceosome‐mediated trans splicing: a problem for gene therapy? Human Gene Therapy 12: 1429–1441.

Krause M and Hirsh D (1987) A trans‐spliced leader sequence on actin mRNA in C. elegans. Cell 49: 753–761.

Murphy WJ, Watkins KP and Agabian N (1986) Identification of a novel Y branch structure as an intermediate in trypanosome mRNA processing: evidence for trans splicing. Cell 47: 517–525.

Reed R (1996) Initial splice‐site recognition and pairing during pre‐mRNA splicing. Current Opinion in Genetics and Development 6: 215–220.

Sutton RE and Boothroyd JC (1986) Evidence for trans splicing in trypanosomes. Cell 47: 527–535.

Wu Q and Maniatis T (1999) A striking organization of a large family of human neural cadherin‐like cell adhesion genes. Cell 97: 779–790.

Zorio DA, Cheng NN, Blumenthal T and Spieth J (1994) Operons as a common form of chromosomal organization in C. elegans. Nature 372: 270–272.

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How to Cite close
Furuyama, Suzanne, and Bruzik, James P(Jan 2006) Trans Splicing. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005973]