Trans-splicing

Trans-splicing is a special form of RNA processing in eukaryotes where exons from two different primary RNA transcripts are joined end to end and ligated.

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.[1]

Trans-splicing can be the mechanism behind certain oncogenic fusion transcripts.[2][3]

Trans-splicing is used by certain microbial organisms, notably protozoa of the Kinetoplastae class to express genes. In these organisms, a capped splice leader RNA is transcribed;[4] simultaneously, genes are transcribed in long polycistrons. The capped splice leader is trans-spliced onto each gene[5] to generate monocistronic capped and polyadenylated transcripts.

References

  1. ↑ Iwasaki R, Kiuchi H, Ihara M, Mori T, Kawakami M, Ueda H (Jul 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.
  2. ↑ Li H, Wang J, Mor G, Sklar J (Sep 2008). "A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells". Science. 321 (5894): 1357–61. doi:10.1126/science.1156725. PMID 18772439.
  3. ↑ Rickman DS, Pflueger D, Moss B, VanDoren VE, Chen CX, de la Taille A, Kuefer R, Tewari AK, Setlur SR, Demichelis F, Rubin MA (Apr 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.
  4. ↑ Campbell, D. A.; Sturm, N. R.; Yu, M. C. (2000-02-01). "Transcription of the kinetoplastid spliced leader RNA gene". Parasitology Today (Personal Ed.). 16 (2): 78–82. doi:10.1016/s0169-4758(99)01545-8. PMID 10652494.
  5. ↑ Liang, Xue-hai; Haritan, Asaf; Uliel, Shai; Michaeli, Shulamit (2003-10-01). "trans and cis splicing in trypanosomatids: mechanism, factors, and regulation". Eukaryotic Cell. 2 (5): 830–840. doi:10.1128/EC.2.5.830-840.2003. PMC 219355. PMID 14555465.

Further reading

  • Dixon RJ, Eperon IC, Samani NJ (Jan 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 (Dec 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 (Aug 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 (Aug 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.


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