Evolutionary origin of SL-addition trans-splicing: still an enigma

doi:10.1016/S0168-9525(01)02499-4

Trends in Genetics

Volume 17, Issue 12, 1 December 2001, Pages 678-680

https://doi.org/10.1016/S0168-9525(01)02499-4 Get rights and content

Abstract

Spliced-leader (SL) trans-splicing is an essential step in pre-mRNA maturation in a variety of lower eukaryotic organisms. However, this processing pathway is absent in mammals, insects, yeast and plants. The patchy phylogenetic distribution of SL trans-splicing is consistent with either ‘multiple gain’ or ‘multiple loss’ evolutionary scenarios. Recent studies show that two additional metazoan phyla carry out SL trans-splicing, significantly increasing its phylogenetic range. However, it remains unclear whether this unusual type of splicing is an ancestral or an acquired trait.

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Cited by (67)

A functional difference between native and horizontally acquired genes in bdelloid rotifers
2016, Gene
Citation Excerpt :
Other organisms that perform SL trans-splicing on at least a proportion of their transcripts include the protists Euglenozoa (Murphy et al., 1986; Sutton and Boothroyd, 1986; Tessier et al., 1991) and Dinoflagellata (Zhang et al., 2007; Bachvaroff and Place, 2008); basal metazoans like some Porifera (Douris et al., 2010), Ctenophora (Derelle et al., 2010; Douris et al., 2010) and Cnidaria (Stover and Steele, 2001; Derelle et al., 2010); protostome metazoans such as chaetognaths (Marletaz et al., 2008; Marletaz and Le Parco, 2008), flatworms (Rajkovic et al., 1990; Davis et al., 1994) and nematodes (Krause and Hirsh, 1987); and some chordates including tunicates (Vandenberghe et al., 2001; Yuasa et al., 2002; Ganot et al., 2004; Satou et al., 2006). There is little conservation of SL sequences, even among closely related species (Davis, 1997; Nilsen, 2001), and therefore a particular SL sequence (or sequences) is characteristic of a species or taxonomic group. Although its function is still unclear, SL trans-splicing has been proposed to be involved in processing, regulation or translation of mRNA (Lasda and Blumenthal, 2011), but also in growth recovery in Caenorhabiditis elegans (Zaslaver et al., 2011) and in nutrient-dependent translational control in the chordate Oikopleura dioica (Danks et al., 2015).
The form of RNA processing known as SL trans-splicing involves the transfer of a short conserved sequence, the spliced leader (SL), from a noncoding SL RNA to the 5′ ends of mRNA molecules. SL trans-splicing occurs in several animal taxa, including bdelloid rotifers (Rotifera, Bdelloidea). One striking feature of these aquatic microinvertebrates is the large proportion of foreign genes, i.e. those acquired by horizontal gene transfer from other organisms, in their genomes. However, whether such foreign genes behave similarly to native genes has not been tested in bdelloids or any other animal. We therefore used a combination of experimental and computational methods to examine whether transcripts of foreign genes in bdelloids were SL trans-spliced, like their native counterparts. We found that many foreign transcripts contain SLs, use similar splice acceptor sequences to native genes, and are able to undergo alternative trans-splicing. However, a significantly lower proportion of foreign mRNAs contains SL sequences than native transcripts. This demonstrates a novel functional difference between foreign and native genes in bdelloids and suggests that SL trans-splicing is not essential for the expression of foreign genes, but is acquired during their domestication.
Intergenically Spliced Chimeric RNAs in Cancer
2016, Trends in Cancer
Citation Excerpt :
Intergenic trans-splicing takes place between two pre-mRNAs transcribed from different gene loci [10,12,38] (Figure 2F). Trans-splicing is a common process in lower species, such as unicellular organisms, nematodes, or trypanosomes, with up to 70% of the genes in these organisms participating in the process [39–42]. The mechanism of trans-splicing in these organisms, specifically known as spliced-leader (SL) trans-splicing, involves transferring a short leader sequence of 15–50 nucleotides from a specialized non-coding RNA molecule to the 5′ end of the mRNAs.
Gene fusions and their encoded products (fusion RNAs and proteins) are viewed as one of the hallmarks of cancer. Traditionally, they were thought to be generated solely by chromosomal rearrangements. However, recent discoveries of trans-splicing and cis-splicing events between neighboring genes suggest that there are other mechanisms to generate chimeric fusion RNAs without corresponding changes in DNA. In addition, chimeric RNAs have been detected in normal physiology, complicating the use of fusions in cancer detection and therapy. By contrast, ‘intergenically spliced’ fusion RNAs represent a new repertoire of biomarkers and therapeutic targets. We review here current knowledge on chimeric RNAs and implications for cancer detection and treatment, and discuss outstanding questions for the advancement of the field.
Molecular cloning and characterization of SL3: A stem cell-specific SL RNA from the planarian Schmidtea mediterranea
2014, Gene
Citation Excerpt :
Moreover in vitro and in vivo reporter assays in nematodes and schistosomes have suggested that SL and non-SL mRNAs do not likely display significant differences in translational efficiency and stability (Cheng et al., 2006, 2007; Lall et al., 2004; Wallace et al., 2010). These limitations in understanding the effect of trans-splicing on target mRNAs not only preclude a comprehension of the phenomenon per se, but also prevent us from gaining much needed insight about its evolutionary history (Douris et al., 2010; Nilsen, 2001). Hence, efforts to address the biological significance of SL trans-splicing in metazoans must extend the interrogation of this process to a greater number of phyla, and consequently, diverse biological contexts.
Spliced leader (SL) trans-splicing is a biological phenomenon, common among many metazoan taxa, consisting in the transfer of a short leader sequence from a small SL RNA to the 5′ end of a subset of pre-mRNAs. While knowledge of the biochemical mechanisms driving this process has accumulated over the years, the functional consequences of such post-transcriptional event at the organismal level remain unclear. In addition, the fact that functional analyses have been undertaken mainly in trypanosomes and nematodes leaves a somehow fragmented picture of the possible biological significance and evolution of SL trans-splicing in eukaryotes. Here, we analyzed the spatial expression of SL RNAs in the planarian flatworm Schmidtea mediterranea, with the goal of identifying novel developmental paradigms for the study of trans-splicing in metazoans. Besides the previously identified SL1 and SL2, S. mediterranea expresses a third SL RNA described here as SL3. While, SL1 and SL2 are collectively expressed in a broad range of planarian cell types, SL3 is highly enriched in a subset of the planarian stem cells engaged in regenerative responses. Our findings provide new opportunities to study how trans-splicing may regulate the phenotype of a cell.
Putative alternative trans-splicing of leukocyte adhesion-GPCR pre-mRNAs generates functional chimeric receptors
2008, FEBS Letters
The EGF-TM7 receptors, a subfamily of adhesion-GPCRs mostly restricted to leukocytes, are known to express multiple functional protein isoforms through extensive alternative cis-splicing. Here, we demonstrate that EGF-TM7 pre-mRNAs also undergo the rare trans-splicing, leading to the generation of functional chimeric receptors. RT-PCR and in silico analyses of EMR2 transcripts identified unique fragments containing the EGF-like motif 3 of a closely related EGF-TM7 gene, CD97, in addition to the alternative cis-spliced products. The sequence swapping is restricted to the EGF-3 exon, generating unique EMR2(1-2-3^∗-5) and EMR2(1-2-3^∗-4-5) molecules, which are functional in ligand-binding as the wild-type EMR2(1-2-3-4-5) and CD97(1-2-3-4-5) receptors. Our results suggest that human leukocytes employ trans-splicing as well as cis-splicing to increase the repertoire of functional adhesion-GPCRs.
Temperature-dependent structural variability of RNAs: Spliced leader RNAS and their evolutionary history
2010, Journal of Bioinformatics and Computational Biology
A PCR-based method for the diagnosis of Enterobius vermicularis in stool samples, specifically designed for clinical application
2022, Frontiers in Microbiology

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Trends in Genetics

Abstract

References (17)

Molecular biology of protozoan and helminth parasites

Spliced leader RNA trans-splicing in metazoa

Parasitol. Today

The role of intron structures in trans-splicing and cap 4 formation for the Leishmania spliced leader RNA

J. Biol. Chem.

Evolutionary fates and origins of U12-Type introns

Mol. Cell

Trans-splicing of pre-mRNA in plants, animals, and protists

FASEB J.

Trans-splicing

mRNA 5′-leader trans-splicing in the chordates

Genes Dev.

Trans-spliced leader addition of mRNAs in a cnidarian

Proc. Natl. Acad. Sci. U. S. A.

Cited by (67)

A functional difference between native and horizontally acquired genes in bdelloid rotifers

Intergenically Spliced Chimeric RNAs in Cancer

Molecular cloning and characterization of SL3: A stem cell-specific SL RNA from the planarian Schmidtea mediterranea

Putative alternative trans-splicing of leukocyte adhesion-GPCR pre-mRNAs generates functional chimeric receptors

Temperature-dependent structural variability of RNAs: Spliced leader RNAS and their evolutionary history

A PCR-based method for the diagnosis of Enterobius vermicularis in stool samples, specifically designed for clinical application

Trends in Genetics

Research updateEvolutionary origin of SL-addition trans-splicing: still an enigma

Abstract

Parasitol. Today

J. Biol. Chem.

Mol. Cell

Trans-splicing of pre-mRNA in plants, animals, and protists

FASEB J.

Trans-splicing

mRNA 5′-leader trans-splicing in the chordates

Genes Dev.

Trans-spliced leader addition of mRNAs in a cnidarian

Proc. Natl. Acad. Sci. U. S. A.

Research update
Evolutionary origin of SL-addition trans-splicing: still an enigma