Trans-splicing

As a trans-splicing, the joining of exons of different mRNAs is called. In contrast to the normal cis -splicing is therefore possible to exons of different RNAs, but which may come from the same gene linked. The "classical " trans -splicing occurs in trypanosomes and nematodes, besides some cases of trans -splicing were discovered in humans.

" Classic " trans -splicing in trypanosomes and nematodes

Kinetoplastida, which include the causative agent of sleeping sickness, Chagas disease and nagana include, in particular, Trypanosoma brucei brucei, are the classic model organisms for the trans -splicing in the strict sense. These organisms produce in transcription similar to the bacteria a polycistronic transcript are released from the individual genes through the trans - splicing. This reaction takes place in a special type spliceosome, in which the U1 snRNP by the " Spliced ​​- Leader" so-called (SL ) snRNP is replaced. Unlike the U1 snRNA, the spliced ​​leader RNA to become depleted in the splicing reaction, since its 5 'end contains a Miniexon, which later constitutes the mRNA with the exon of the polycistronic transcript (see adjacent figure). The Miniexon the SL RNA also contains the AUG start codon, so it is essential for a complete mRNA with the correct open reading frame.

In addition to the trans -splicing in trypanosomes was only one " classic " cis- intron discovered in the gene for the poly -A polymerase, which means that trypanosomes contain a U1 snRNP, but only in extremely small amounts ( this was also recently characterized).

Trans-splicing in the narrow sense was also observed in Ciona intestinalis and nematodes, but it lacks in almost all other organisms.

Trans -splicing in humans

In some cases people of the trans - splicing have been reported. Unlike in trypanosomes no Spliced ​​- Leader - snRNP, so no trans -splicing exist here but in the " classical" sense. Rather, two pre-mRNAs of the same gene are processed together, which do not differ in all previously reported cases in sequence from each other (hence trans -splicing, because two independent RNAs are spliced ​​together ). This results in a duplication of an exon in the mRNA later. However, this process occurs in humans is extremely rare ( the latest figures speak of two "real" examples, which are only found with 15 ESTs in the databases ), but still broke the reports of a hot discussion whether not taking advantage of this process ways could be found to treat hereditary diseases ( first efforts have been made to the tau gene that plays a role in dementias such as Alzheimer 's disease). Here too, but - as with a variety of other innovative, but also in long-known therapeutic strategies - the problem of the delivery, the active ingredient ', which is an RNA in this case.

Also in cyanobacteria ( see Article intein, last paragraph) trans-splicing plays a role.

Credentials

• Y. Satou: Genomic overview of mRNA 5' -leader trans - splicing in the ascidian Ciona intestinalis. In: Nucleic Acids Research. 34, 2006, pp. 3378-3388, doi: 10.1093/nar/gkl418, PMC 1488885 (Free full text ).

• Genetics