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''Trans''-splicing is a special form of RNA processing where
exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
s from two different primary RNA transcripts are joined end to end and ligated. It is usually found in
eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s and mediated by the spliceosome, although some bacteria and archaea also have "half-genes" for
tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...
s.


Genic ''trans''-splicing

Whereas "normal" (''cis''-)splicing processes a single molecule, ''trans''-splicing generates a single RNA transcript from multiple separate
pre-mRNA A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by Transcription (genetics), transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcript ...
s. This phenomenon can be exploited for molecular therapy to address mutated gene products. Genic trans-splicing allows variability in RNA diversity and increases proteome complexity.


Oncogenesis

While some fusion transcripts occur via ''trans''-splicing in normal human cells, ''trans''-splicing can also be the mechanism behind certain oncogenic fusion transcripts.


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. The capped splice leader is ''trans''-spliced onto each gene to generate monocistronic capped and polyadenylated transcripts. These early-diverging eukaryotes use few
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
s, and the spliceosome they possess show some unusual variations in their structure assembly. They also possess multiple eIF4E isoforms with specialized roles in capping. 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. Some other eukaryotes, notably among dinoflagellates,
sponges Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a basal clade and a sister taxon of the diploblasts. They are sessile filter feeders that are bound to the seabed, and ar ...
,
nematodes The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (he ...
,
cnidarians Cnidaria ( ) is a phylum under kingdom Animalia containing over 11,000 species of aquatic invertebrates found both in fresh water, freshwater and marine environments (predominantly the latter), including jellyfish, hydroid (zoology), hydroids, ...
,
ctenophores Ctenophora (; : ctenophore ) is a phylum of marine invertebrates, commonly known as comb jellies, that marine habitats, inhabit sea waters worldwide. They are notable for the groups of cilia they use for swimming (commonly referred to as "combs ...
, flatworms,
crustaceans Crustaceans (from Latin meaning: "those with shells" or "crusted ones") are invertebrate animals that constitute one group of Arthropod, arthropods that are traditionally a part of the subphylum Crustacea (), a large, diverse group of mainly aquat ...
, chaetognaths,
rotifers The rotifers (, from Latin 'wheel' and 'bearing'), sometimes called wheel animals or wheel animalcules, make up a phylum (Rotifera ) of microscopic and near-microscopic pseudocoelomate animals. They were first described by Rev. John Harris ...
, and tunicates also use more or less frequently the SL ''trans''-splicing. 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. The SL ''trans''-splicing functions in 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.


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. 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.


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.


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.


See also

* Chimera (EST)


References


Further reading

* * * * {{refend RNA Spliceosome RNA splicing