Trans-splicing

Source: Wikipedia, the free encyclopedia.

Trans-splicing is a special form of

tRNAs.[1]

Genic trans-splicing

Whereas "normal"

pre-mRNAs. This phenomenon can be exploited for molecular therapy to address mutated gene products.[2] Genic trans-splicing allows variability in RNA diversity and increases proteome complexity.[3]

Oncogenesis

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.[4][5]

SL trans-splicing

Spliced leader (SL) trans-splicing is used by certain microorganisms, notably protists of the

Kinetoplastea class to express genes. In these organisms, a capped splice leader RNA is transcribed, and simultaneously, genes are transcribed in long polycistrons.[6] The capped splice leader is trans-spliced onto each gene to generate monocistronic capped and polyadenylated transcripts.[7] These early-diverging eukaryotes use few introns, and the spliceosome they possess show some unusual variations in their structure assembly.[7][8] They also possess multiple eIF4E isoforms with specialized roles in capping.[9] The spliced leader sequence is highly conserved in lower species that undergo trans-splicing. Such as trypanosomes. While the spliced leader's role is not known in the cell, it's thought to be involved in translation initiation. In C.elegans, the splicing of the sequence leader occurs close to the initiation codon. Some scientists also suggest the sequence is required for cell viability. In Ascaris, the spliced leader sequence is needed to the RNA gene can be transcribed. The Spliced leader sequence may be responsible for initiation, mRNA localization, and translation initiation or inhibition.[10]

Some other eukaryotes, notably among

tunicates also use more or less frequently the SL trans-splicing.[1][11] 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.[12]

The SL trans-splicing functions in the resolution of

open reading frames.[13][14]

Mechanism

Trans-splicing is characterized by the joining of two separate exons transcribed RNAs. The signal for this splicing is the outron at the 5’ end of the mRNA, in the absence of a functional 5’ splice site upstream. When the 5’ outron in spliced, the 5’ splice site of the spliced leader RNA is branched to the outron and forms an intermediate.[10] This step results in a free spliced leader exon. The exon is then spliced to the first exon on the pre-mRNA and the intermediate is released. Trans-splicing differs from cis-splicing in that there is no 5' splice site on the pre-mRNA. Instead the 5' splice site is provided by the SL sequence.[14]

Trans-splicing between sense and anti-sense strands

As a result of the sense strand undergoing transcription, a pre-mRNA is formed that complements the sense strand. The anti-sense strand is also transcribed resulting in a complementary pre-mRNA strand. The exons from the two transcripts are spliced together to form a chimeric mRNA.[15]

Alternative Trans-splicing

Alternative trans-splicing includes intragenic trans-splicing and intergenic trans-splicing. Intragenic trans-splicing involves duplication of exons in the pre-mRNA. Intergenic trans-splicing is characterized by the splicing together of exons formed form the pre-mRNA of two different genes, resulting in trans-genic mRNA.[16]

See also

  • Chimera (EST)

References

  1. ^
    PMID 26966239
    .
  2. PMID 19409879
    .
  3. S2CID 209567118
    .
  4. S2CID 13605087
    .
  5. PMID 19293179
    .
  6. PMID 10652494
    .
  7. ^
    PMID 14555465
    .
  8. PMID 20581293
    .
  9. PMID 29077018
    .
  10. ^
    PMID 17099225
    .
  11. S2CID 209567118
    .
  12. PMID 20212022
    .
  13. PMID 11953307
    .
  14. ^
    S2CID 9864778
    .
  15. PMID 26966239
    .
  16. S2CID 10335534
    .

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=Trans-splicing&oldid=1209545365"