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[
Curr Opin Genet Dev,
2000]
Repeated copies of genes, whether in tandem or dispersed, are often recognized by the cell and silenced. Tandem repeat silencing is associated with a heterochromatin-like complex. Dispersed gene silencing can be mediated by the repressive Polycomb Group complex or involve post-transcriptional silencing presumably involving double-stranded RNA. The I retrotransposable element in Drosophila appears to be susceptible to dispersed gene silencing, potentially by both post-transcriptional and transcriptional processes. Some mutations that eliminate RNA interference in Caenorhabditis elegans result in the mobilization of many transposons and two of these mutations desilence tandem repeats in the germline. One challenge for the future is to determine the nature of any relationship between post-transcriptionally and transcriptionally based mechanisms. The silencing mechanisms potentially act as a protection against high expression of transposons and viruses.
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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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Biochim Biophys Acta,
2008]
The Schizosaccharomyces pombe cytoplasmic protein Cid1 acts as a poly(U) polymerase (PUP). Polyadenylated actin mRNA, a target of this activity, is uridylated upon arrest in S phase and is likely to be one of many such Cid1 targets. This RNA uridylation pathway appears to be conserved, as Cid1 orthologs in Arabidopsis thaliana, Caenorhabditis elegans and humans display PUP activity either in vitro or in Xenopus laevis oocytes. Here, we review the literature on Cid1, other PUPs and uridylation, a conserved and previously under-appreciated mechanism of RNA regulation.
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Mech Dev,
2017]
Gonad morphogenesis in the nematode C. elegans is guided by two leader cells, the distal tip cells (DTC). The DTCs migrate along a stereotyped path, executing two 90 turns before stopping at the midpoint of the animal. This migratory path determines the double-U shape of the adult gonad, therefore, the path taken by the DTCs can be inferred from the final shape of the organ. In this review, we focus on the mechanism by which the DTC executes the first 90 turn from the ventral to dorsal side of the animal, and how it finds its correct stopping place at the midpoint of the animal. We discuss the role of heterochronic genes in coordinating DTC migration with larval development, the role of feedback loops and miRNA regulation in phenotypic robustness, and the role of RNA binding proteins in the cessation of DTC migration.
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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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[
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.