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. 2013 Oct 11:4:199.
doi: 10.3389/fgene.2013.00199. eCollection 2013.

The spliced leader trans-splicing mechanism in different organisms: molecular details and possible biological roles

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The spliced leader trans-splicing mechanism in different organisms: molecular details and possible biological roles

Mainá Bitar et al. Front Genet. .

Abstract

THE SPLICED LEADER (SL) IS A GENE THAT GENERATES A FUNCTIONAL NCRNA THAT IS COMPOSED OF TWO REGIONS: an intronic region of unknown function (SLi) and an exonic region (SLe), which is transferred to the 5' end of independent transcripts yielding mature mRNAs, in a process known as spliced leader trans-splicing (SLTS). The best described function for SLTS is to solve polycistronic transcripts into monocistronic units, specifically in Trypanosomatids. In other metazoans, it is speculated that the SLe addition could lead to increased mRNA stability, differential recruitment of the translational machinery, modification of the 5' region or a combination of these effects. Although important aspects of this mechanism have been revealed, several features remain to be elucidated. We have analyzed 157 SLe sequences from 148 species from seven phyla and found a high degree of conservation among the sequences of species from the same phylum, although no considerable similarity seems to exist between sequences of species from different phyla. When analyzing case studies, we found evidence that a given SLe will always be related to a given set of transcripts in different species from the same phylum, and therefore, different SLe sequences from the same species would regulate different sets of transcripts. In addition, we have observed distinct transcript categories to be preferential targets for the SLe addition in different phyla. This work sheds light into crucial and controversial aspects of the SLTS mechanism. It represents a comprehensive study concerning various species and different characteristics of this important post-transcriptional regulatory mechanism.

Keywords: RNA secondary structure; RNA sequence analysis; non-coding RNAs; spliced-leader; trans-splicing.

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Figures

Figure 1
Figure 1
Different splicing mechanisms. (A) Variations of cis- and trans-splicing processes. (B) The spliced leader trans-splicing mechanism. This panel depicts the overall SLTS mechanism, in which an invariant exon (the SLe) is added to an unrelated, independently produced transcript, yielding a mature mRNA. Cis-splicing is also represented for comparison. The SLe molecule contains a hypermodified cap, whereas the SLi usually harbors an Sm-protein binding site.
Figure 2
Figure 2
Methodological workflow. The figure schematically describes the main steps performed in this work as a fluxogram.
Figure 3
Figure 3
Sequence logos generated from the alignment of all SLe sequences from each phylum showing sequence lengths in numbers and the frequency of the four nucleotides in each position.
Figure 4
Figure 4
Structures of SL genes. Secondary structures were generated for SL genes of different phyla and a visual analysis of these structures point to a conserved Y-shape for the SL molecule. The backbones of the structures are displayed to the right for a simpler view.
Figure 5
Figure 5
The classification of SLe-containing transcripts from all analyzed species. Pie charts are presented for each phylum individually (upper charts) and for the entire set of 455 transcripts (bottom chart). Functional classes are represented by color, and the arrow indicates the direction that corresponds to the legend. The most populated class for each phylum is labeled by name.

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