''Trans''-splicing is a special form of
RNA processing
Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, f ...
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 sequen ...
s from two different primary
RNA transcripts are joined end to end and
ligated. It is usually found in
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s and mediated by the
spliceosome
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs ( snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specif ...
, although some bacteria and archaea also have "half-genes" for
tRNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
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 of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs ...
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 transcript Fusion transcript is a chimeric RNA encoded by a fusion gene or by two different genes by subsequent trans-splicing. Certain fusion transcripts are commonly produced by cancer
Cancer is a group of diseases involving abnormal cell growth wi ...
s.
SL ''trans''-splicing
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. 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., gene. ...
s, and the spliceosome they possess show some unusual variations in their structure assembly.
[ They also possess multiple ]eIF4E
Eukaryotic translation initiation factor 4E, also known as eIF4E, is a protein that in humans is encoded by the ''EIF4E'' gene.
Structure and function
Most eukaryotic cellular mRNAs are blocked at their 5'-ends with the 7-methyl-guanosine f ...
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.dinoflagellates
The dinoflagellates (Greek δῖνος ''dinos'' "whirling" and Latin ''flagellum'' "whip, scourge") are a monophyletic group of single-celled eukaryotes constituting the phylum Dinoflagellata and are usually considered algae. Dinoflagellates a ...
, sponges
Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through ...
, nematodes
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...
, cnidarians
Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter.
Their distinguishing feature is cnidocytes, specialized cells that th ...
, ctenophores
Ctenophora (; ctenophore ; ) comprise a phylum of marine invertebrates, commonly known as comb jellies, that inhabit sea waters worldwide. They are notable for the groups of cilia they use for swimming (commonly referred to as "combs"), a ...
, flatworms
The flatworms, flat worms, Platyhelminthes, or platyhelminths (from the Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") are a phylum of relatively simple bilaterian, unsegment ...
, crustaceans
Crustaceans (Crustacea, ) form a large, diverse arthropod taxon which includes such animals as decapods, seed shrimp, branchiopods, fish lice, krill, remipedes, isopods, barnacles, copepods, amphipods and mantis shrimp. The crustacean group ...
, chaetognaths
The Chaetognatha or chaetognaths (meaning ''bristle-jaws'') are a phylum of predatory marine worms that are a major component of plankton worldwide. Commonly known as arrow worms, about 20% of the known Chaetognatha species are benthic, and ca ...
, rotifers
The rotifers (, from the Latin , "wheel", and , "bearing"), commonly 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 H ...
, and tunicates
A tunicate is a marine invertebrate animal, a member of the subphylum Tunicata (). It is part of the Chordata, a phylum which includes all animals with dorsal nerve cords and notochords (including vertebrates). The subphylum was at one time ca ...
also use more or less frequently the SL ''trans''-splicing.polycistronic
A cistron is an alternative term for "gene". The word cistron is used to emphasize that genes exhibit a specific behavior in a cis-trans test; distinct positions (or loci) within a genome are cistronic.
History
The words ''cistron'' and ''gene ...
transcripts of operon
In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
s into individual 5'-capped mRNAs. This processing is achieved when the outron
An outron is a nucleotide sequence at the 5' end of the primary transcript of a gene that is removed by a special form of RNA splicing during maturation of the final RNA product. Whereas intron sequences are located inside the gene, outron sequ ...
s are ''trans''-spliced to unpaired, downstream acceptor sites adjacent to cistron open reading frames
In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
.
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.
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)
In molecular biology, and more importantly high-throughput DNA sequencing, a chimera is a single DNA sequence originating when multiple transcripts or DNA sequences get joined. It can occur in various contexts. Chimeric reads are generally con ...
References
Further reading
*
*
*
*
RNA
Spliceosome
RNA splicing
{{genetics-stub