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Trans-splicing is a special form of RNA processing where exons from two different primary RNA transcripts are joined end to end and ligated. It is usually found in eukaryotes and mediated by the spliceosome, although some bacteria and archaea also have "half-genes" for tRNAs.[1]

Genic trans-splicingEdit

Whereas "normal" (cis-)splicing processes a single molecule, trans-splicing generates a single RNA transcript from multiple separate pre-mRNAs. This phenomenon can be exploited for molecular therapy to address mutated gene products.[2]

OncogenesisEdit

While some fusion transcripts occur via trans-splicing in normal human cells,[1] trans-splicing can also be the mechanism behind certain oncogenic fusion transcripts.[3][4]

SL trans-splicingEdit

Spliced leader (SL) trans-splicing is used by certain microorganisms, notably protists of the Kinetoplastae class to express genes. In these organisms, a capped splice leader RNA is transcribed, and simultaneously, genes are transcribed in long polycistrons.[5] The capped splice leader is trans-spliced onto each gene to generate monocistronic capped and polyadenylated transcripts.[6] These early-diverging eukaryotes use few introns, and the spliceosome they possess show some unusual variations in their structure assembly.[6][7] They also possess multiple eIF4E isoforms with specialized roles in capping.[8]

Some other eukaryotes, notably among dinoflagellates, sponges, nematodes, cnidarians, ctenophores, flatworms, crustaceans, chaetognaths, rotifers, and tunicates also use more or less frequently the SL trans-splicing.[1][9] In the tunicate Ciona intestinalis, the extent of SL trans-splicing is better described by a quantitative view recognising frequently and infrequently trans-spliced genes rather than a binary and conventional categorisation of trans-spliced versus non-trans-spliced genes.[10]

One function of the SL trans-splicing is the resolution of polycistronic transcripts of operons into individual 5'-capped mRNAs. This processing is achieved when the outrons are trans-spliced to unpaired, downstream acceptor sites adjacent to cistron open reading frames.[11][12]

ReferencesEdit

  1. ^ a b c Lei Q, Li C, Zuo Z, Huang C, Cheng H, Zhou R (March 2016). "Evolutionary Insights into RNA trans-Splicing in Vertebrates". Genome Biology and Evolution. 8 (3): 562–77. doi:10.1093/gbe/evw025. PMC 4824033. PMID 26966239.
  2. ^ Iwasaki R, Kiuchi H, Ihara M, Mori T, Kawakami M, Ueda H (July 2009). "Trans-splicing as a novel method to rapidly produce antibody fusion proteins". Biochemical and Biophysical Research Communications. 384 (3): 316–21. doi:10.1016/j.bbrc.2009.04.122. PMID 19409879.
  3. ^ Li H, Wang J, Mor G, Sklar J (September 2008). "A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells". Science. 321 (5894): 1357–61. Bibcode:2008Sci...321.1357L. doi:10.1126/science.1156725. PMID 18772439.
  4. ^ Rickman DS, Pflueger D, Moss B, VanDoren VE, Chen CX, de la Taille A, et al. (April 2009). "SLC45A3-ELK4 is a novel and frequent erythroblast transformation-specific fusion transcript in prostate cancer". Cancer Research. 69 (7): 2734–8. doi:10.1158/0008-5472.CAN-08-4926. PMC 4063441. PMID 19293179.
  5. ^ Campbell DA, Sturm NR, Yu MC (February 2000). "Transcription of the kinetoplastid spliced leader RNA gene". Parasitology Today. 16 (2): 78–82. doi:10.1016/s0169-4758(99)01545-8. PMID 10652494.
  6. ^ a b Liang XH, Haritan A, Uliel S, Michaeli S (October 2003). "trans and cis splicing in trypanosomatids: mechanism, factors, and regulation". Eukaryotic Cell. 2 (5): 830–40. doi:10.1128/EC.2.5.830-840.2003. PMC 219355. PMID 14555465.
  7. ^ Günzl A (August 2010). "The pre-mRNA splicing machinery of trypanosomes: complex or simplified?". Eukaryotic Cell. 9 (8): 1159–70. doi:10.1128/EC.00113-10. PMC 2918933. PMID 20581293.
  8. ^ Freire ER, Sturm NR, Campbell DA, de Melo Neto OP (October 2017). "The Role of Cytoplasmic mRNA Cap-Binding Protein Complexes in Trypanosoma brucei and Other Trypanosomatids". Pathogens. 6 (4): 55. doi:10.3390/pathogens6040055. PMC 5750579. PMID 29077018.
  9. ^ Lasda EL, Blumenthal T (2011-05-01). "Trans-splicing". Wiley Interdisciplinary Reviews. RNA. 2 (3): 417–34. doi:10.1002/wrna.71. PMID 21957027.
  10. ^ Matsumoto J, Dewar K, Wasserscheid J, Wiley GB, Macmil SL, Roe BA, et al. (May 2010). "High-throughput sequence analysis of Ciona intestinalis SL trans-spliced mRNAs: alternative expression modes and gene function correlates". Genome Research. 20 (5): 636–45. doi:10.1101/gr.100271.109. PMC 2860165. PMID 20212022.
  11. ^ Clayton, Christine E. (2002-04-15). "Life without transcriptional control? From fly to man and back again". The EMBO Journal. 21 (8): 1881–1888. doi:10.1093/emboj/21.8.1881. ISSN 1460-2075. PMC 125970. PMID 11953307.
  12. ^ Blumenthal, Thomas; Gleason, Kathy Seggerson (February 2003). "Caenorhabditis elegans operons: form and function". Nature Reviews Genetics. 4 (2): 110–118. doi:10.1038/nrg995. ISSN 1471-0056. PMID 12560808.

Further readingEdit

  • Dixon RJ, Eperon IC, Samani NJ (January 2007). "Complementary intron sequence motifs associated with human exon repetition: a role for intragenic, inter-transcript interactions in gene expression". Bioinformatics. 23 (2): 150–5. doi:10.1093/bioinformatics/btl575. PMID 17105720.
  • Yang Y, Walsh CE (December 2005). "Spliceosome-mediated RNA trans-splicing". Molecular Therapy. 12 (6): 1006–12. doi:10.1016/j.ymthe.2005.09.006. PMID 16226059.
  • Coady TH, Shababi M, Tullis GE, Lorson CL (August 2007). "Restoration of SMN function: delivery of a trans-splicing RNA re-directs SMN2 pre-mRNA splicing". Molecular Therapy. 15 (8): 1471–8. doi:10.1038/sj.mt.6300222. PMID 17551501.
  • Wally V, Murauer EM, Bauer JW (August 2012). "Spliceosome-mediated trans-splicing: the therapeutic cut and paste". The Journal of Investigative Dermatology. 132 (8): 1959–66. doi:10.1038/jid.2012.101. PMID 22495179.