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[
Biochem Soc Trans,
2010]
Spliced leader trans-splicing occurs in many primitive eukaryotes including nematodes. Most of our knowledge of trans-splicing in nematodes stems from the model organism Caenorhabditis elegans and relatives, and from work with Ascaris. Our investigation of spliced leader trans-splicing in distantly related Dorylaimia nematodes indicates that spliced-leader trans-splicing arose before the nematode phylum and suggests that the spliced leader RNA gene complements in extant nematodes have evolved from a common ancestor with a diverse set of spliced leader RNA genes.
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WormBook,
2005]
About 70% of C. elegans mRNAs are trans-spliced to one of two 22 nucleotide spliced leaders. SL1 is used to trim off the 5'' ends of pre-mRNAs and replace them with the SL1 sequence. This processing event is very closely related to cis-splicing, or intron removal. The SL1 sequence is donated by a 100 nt small nuclear ribonucleoprotein particle (snRNP). This snRNP is structurally and functionally related to the U snRNAs (U1, U2, U4, U5 and U6) that play key roles in intron removal and trans-splicing, except that it is consumed in the process of splicing. More than half of C. elegans pre-mRNAs are subject to SL1 trans-splicing. About 30% are not trans-spliced at all. The remaining genes are trans-spliced by SL2. These genes are all downstream genes in closely spaced gene clusters similar to bacterial operons. They are transcribed from a promoter at the 5'' end of the cluster of between 2 and 8 genes. This transcription makes a polycistronic pre-mRNA that is co-transcriptionally processed by cleavage and polyadenylation at the 3'' end of each gene, and this event is closely coupled to the SL2 trans-splicing event that occurs only ~100 nt further downstream. Recent studies on the mechanism of SL2 trans-splicing have revealed that one of the 3'' end formation proteins, CstF, interacts with the only protein known to be specific to the SL2 snRNP. The operons contain primarily genes whose products are needed for mitochondrial function and the basic machinery of gene expression: transcription, splicing and translation. Many operons contain genes whose products are known to function together. This presumably provides co-regulation of these proteins by producing a single RNA that encodes both.
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[
Experimental Parasitology,
1989]
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[
WormBook,
2012]
About 70% of C. elegans mRNAs are trans-spliced to one of two 22 nucleotide spliced leaders. SL1 is used to trim off the 5' ends of pre-mRNAs and replace them with the SL1 sequence. This processing event is very closely related to cis-splicing, or intron removal. The SL1 sequence is donated by a 100 nt small nuclear ribonucleoprotein particle (snRNP), the SL1 snRNP. This snRNP is structurally and functionally similar to the U snRNAs (U1, U2, U4, U5 and U6) that play key roles in intron removal and trans-splicing, except that the SL1 snRNP is consumed in the process. More than half of C. elegans pre-mRNAs are subject to SL1 trans-splicing, whereas ~30% are not trans-spliced. The remaining genes are trans-spliced by SL2, which is donated by a similar snRNP, the SL2 snRNP. SL2 recipients are all downstream genes in closely spaced gene clusters similar to bacterial operons. They are transcribed from a promoter at the 5' end of the cluster of between 2 and 8 genes. This transcription makes a polycistronic pre-mRNA that is co-transcriptionally processed by cleavage and polyadenylation at the 3' end of each gene, and this event is closely coupled to the SL2 trans-splicing event that occurs only ~100 nt further downstream. SL2 trans-splicing requires a sequence between the genes, the Ur element, that likely base pairs with the 5' splice site on the SL2 snRNP, in a manner analogous to the interaction between the 5' splice site in cis-splicing with the U1 snRNP. The key difference is that in trans-splicing, the snRNP contains the 5' splice site, whereas in cis-splicing the pre-mRNA does. Some operons, termed "hybrid operons", contain an additional promoter between two genes that can express the downstream gene or genes with a developmental profile that is different from that of the entire operon. The operons contain primarily genes required for rapid growth, including genes whose products are needed for mitochondrial function and the basic machinery of gene expression. Recent evidence suggests that RNA polymerase is poised at the promoters of growth genes, and operons allow more efficient recovery from growth-arrested states, resulting in reduction in the need for this cache of inactive RNA polymerase.
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[
Mol Biochem Parasitol,
1995]
5'-end maturation of messenger RNAs via acquisition of a trans-spliced leader sequence occurs in several primitive eukaryotes, some of which are parasitic. This type of trans-splicing proceeds though a two-step reaction pathway directly analogous to that of cis-splicing and like cis-splicing it requires multiple U snRNP cofactors. This minireview attempts to provide a brief synopsis of our current understanding of the evolution and biological significance of trans-splicing. Progress in deciphering the mechanism of trans-splicing, particularly as it relates to current models of cis-splicing, is also discussed.
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Mitochondrion,
2020]
Mitochondria are key components of eukaryotic cells, so their proper functioning is monitored via different mitochondrial signalling responses. One of these mitochondria-to-nuclear 'retrograde' responses to maintain mitochondrial homeostasis is the mitochondrial unfolded protein response (UPR<sup>mt</sup>), which can be activated by a variety of defects including blocking mitochondrial translation, respiration, protein import or transmembrane potential. Although UPR<sup>mt</sup> was first reported in cultured mammalian cells, this signalling pathway has also been extensively studied in the nematode Caenorhabditis elegans. In yeast, there are no published studies focusing on UPR<sup>mt</sup> in a strict sense, but other unfolded protein responses (UPR) that appear related to UPR<sup>mt</sup> have been described, such as the UPR activated by protein mistargeting (UPR<sup>am</sup>) and mitochondrial compromised protein import response (mitoCPR). In plants, very little is known about UPR<sup>mt</sup> and only recently some of the regulators have been identified. In this paper, we summarise and compare the current knowledge of the UPR<sup>mt</sup> and related responses across eukaryotic kingdoms: animals, fungi and plants. Our comparison suggests that each kingdom has evolved its own specific set of regulators, however, the functional categories represented among UPR<sup>mt</sup>-related target genes appear to be largely overlapping. This indicates that the strategies for preserving proper mitochondrial functions are partially conserved, targeting mitochondrial chaperones, proteases, import components, dynamics and stress response, but likely also non-mitochondrial functions including growth regulators/hormone balance and amino acid metabolism. We also identify homologs of known UPR<sup>mt</sup> regulators and responsive genes across kingdoms, which may be interesting targets for future research.
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[
BioEssays,
1993]
In trans-splicing, the pre-mRNA products of two different genes are spliced together to form a single, mature mRNA. In one type of trans-splicing, pre-mRNAs of many different genes receive a single, short leader, called spliced leader or SL. This type of trans-splicing was first discovered in the primitive eukaryotes, the trypanosomes, where it is apparently the only kind of nuclear mRNA splicing. Subsequently, it was discovered in nematodes (round worms), trematodes (flat worms), and euglena. Although this type of trans-splicing has never been found in any of the other well-studied organisms, Bruzik and Maniatis have recently reported that mammalian cells are capable of performing the reaction when they are provided with the appropriate pre-mRNAs.
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[
Trends Genet,
1995]
Caenorhabditis elegans engages in three distinct versions of nuclear pre-mRNA splicing: cis-splicing of introns and two kinds of trans-splicing that result in the addition of two different spliced leaders onto mRNAs. One leader (SL1) is used near the 5' ends of pre-mRNAs while the other (SL2) is used at internal trans-splice sites of polycistronic pre-mRNAs. Here, I consider bow these three types of splicing event are faithfully carried out.
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[
Parasitol Today,
1996]
Spliced leader trans-splicing is a form of RNA processing originally described and studied in parasitic kinetoplastida. This mechanism of gene expression also occurs in parasitic and free-living metazoa. In this review, Dick Davis describes current knowledge of the distribution, substrates, specificity and functional significance of trans-splicing in metazoa.
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[
Wiley Interdiscip Rev RNA,
2011]
Trans-splicing is the joining together of portions of two separate pre-mRNA molecules. The two distinct categories of spliceosomal trans-splicing are genic trans-splicing, which joins exons of different pre-mRNA transcripts, and spliced leader (SL) trans-splicing, which involves an exon donated from a specialized SL RNA. Both depend primarily on the same signals and components as cis-splicing. Genic trans-splicing events producing protein-coding mRNAs have been described in a variety of organisms, including Caenorhabditis elegans and Drosophila. In mammalian cells, genic trans-splicing can be associated with cancers and translocations. SL trans-splicing has mainly been studied in nematodes and trypanosomes, but there are now numerous and diverse phyla (including primitive chordates) where this type of trans-splicing has been detected. Such diversity raises questions as to the evolutionary origin of the process. Another intriguing question concerns the function of trans-splicing, as operon resolution can only account for a small proportion of the total amount of SL trans-splicing.