mRNA 5′-leader <i>trans</i>-splicing in the chordates

Vandenberghe, Amanda E.; Meedel, Thomas H.; Hastings, Kenneth E.M.

doi:10.1101/gad.865401

Cited by 138 publications

(138 citation statements)

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“…SL RNAs identified in other systems are predicted to adopt a conserved structure that consists of a stem-loop containing the splice donor dinucleotide, followed by two additional stem-loops that flank a single-stranded region containing a binding site for the Sm protein. The exceptions to this structure are the SL of the flatworm Schistosoma mansoni, in which the second stem-loop is absent (29), and the SL of the ascidian Ciona intestinalis, in which both the second and third stem-loops are absent (1). We have attempted to model the secondary structures of the Hydra SL RNAs by using Version 2.3 of MFOLD (27,28).…”

Section: Sl-a and -B Are Encoded By Genes Located In The 5s Rrna Genementioning

confidence: 99%

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Trans-spliced leader addition to mRNAs in a cnidarian

Stover

Steele

2001

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

108

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Section: Sl-a and -B Are Encoded By Genes Located In The 5s Rrna Genementioning

confidence: 99%

“…To date, SL addition has been identified in three metazoan phyla (Nematoda, Platyhelminthes, and Chordata) (1)(2)(3)(4) and in one unicellular eukaryotic phylum (Sarcomastigophora) (3,(5)(6)(7). No evidence of SL addition has been detected in any intensively studied plants, fungi, insects, echinoderms, or vertebrates.…”

mentioning

confidence: 99%

Trans-spliced leader addition to mRNAs in a cnidarian

Stover

Steele

2001

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

108

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“…Finally, the trans-splice site is at the 59 end of the mRNA, not the pre-mRNA, and thus, the promoter is often not directly adjacent to the gene, but rather upstream of the outron or the entire operon (Blumenthal and Spieth 1996). SL trans-splicing has been reported in many phyla, including trypanosomes, nematodes, and even chordates (Sutton and Boothroyd 1986;Krause and Hirsh 1987;Vandenberghe et al 2001). In 1994, it was estimated that 70% of C. elegans genes were trans-spliced, based on the limited genomic and cDNA sequence data available (Zorio et al 1994).…”

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confidence: 99%

“…SL trans-splicing has been reported in many phyla, including trypanosomes, nematodes, and even chordates (Sutton and Boothroyd 1986;Krause and Hirsh 1987;Vandenberghe et al 2001). In 1994, it was estimated that 70% of C. elegans genes were trans-spliced, based on the limited genomic and cDNA sequence data available (Zorio et al 1994).…”

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A global analysis of C. elegans trans-splicing

Allen¹,

Hillier²,

Waterston³

et al. 2010

Genome Res.

158

256

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Trans-splicing of one of two short leader RNAs, SL1 or SL2, occurs at the 59 ends of pre-mRNAs of many C. elegans genes. We have exploited RNA-sequencing data from the modENCODE project to analyze the transcriptome of C. elegans for patterns of trans-splicing. Transcripts of~70% of genes are trans-spliced, similar to earlier estimates based on analysis of far fewer genes. The mRNAs of most trans-spliced genes are spliced to either SL1 or SL2, but most genes are not transspliced to both, indicating that SL1 and SL2 trans-splicing use different underlying mechanisms. SL2 trans-splicing occurs in order to separate the products of genes in operons genome wide. Shorter intercistronic distance is associated with greater use of SL2. Finally, increased use of SL1 trans-splicing to downstream operon genes can indicate the presence of an extra promoter in the intercistronic region, creating what has been termed a ''hybrid'' operon. Within hybrid operons the presence of the two promoters results in the use of the two SL classes: Transcription that originates at the promoter upstream of another gene creates a polycistronic pre-mRNA that receives SL2, whereas transcription that originates at the internal promoter creates transcripts that receive SL1. Overall, our data demonstrate that >17% of all C. elegans genes are in operons.[Supplemental material is available for this article. The sequence data from this study have been submitted to the NCBI Sequence Read Archive (http://www.ncbi.nlm.nih.gov/Traces/sra/sra.cgi) under accession nos. SRA008646 and SRA003622.] C. elegans uses two RNA processing features that distinguish it from other model organisms. First, the transcripts of many genes are trans-spliced to a spliced leader (SL). Trans-splicing is a process in which an SL replaces the 59 end of a transcript by spliceosomal splicing. The 22-nucleotide (nt) SL is donated by an ;100-nt SL snRNP (small nuclear ribonucleoprotein) to a pre-mRNA with an intron-like region, the outron, containing an unpaired 39 splice site located near the 59 end. The second distinguishing feature is that many genes are transcribed in polycistronic units, known as operons, where a single promoter serves several genes. The operons can be up to eight genes long, and the polycistronic pre-mRNAs are separated into individual cistrons by 39 end formation accompanied by SL trans-splicing.These two features have important implications for C. elegans research. For instance, deletions/insertions within an operon may affect not only the expression of the gene containing the mutation, but also the genes downstream from it in the operon (Cui et al. 2008). Similarly, in a strain with enhanced RNAi sensitivity, RNAi of an operon gene can also affect expression of genes downstream (Guang et al. 2010). Finally, the trans-splice site is at the 59 end of the mRNA, not the pre-mRNA, and thus, the promoter is often not directly adjacent to the gene, but rather upstream of the outron or the entire operon (Blumenthal and Spieth 1996). SL trans-splicing has been repor...

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“…In the metazoans, trans-splicing has been described in free-living or parasitic nematodes (Krause & Hirsh 1987, Blaxter & Liu 1996, in trematodes (Rajkovic et al 1990, Davis et al 1994) and cestodes (Brehm et al 2000) as well as in turbelarians (Davis 1997) of the Platyhelminthes phylum. More recently, this form of RNA processing has been described in Hydra, a member of Cnidaria phylum (Stover & Steele 2001) and, surprisingly in two members of the Urochordata subphylum of chordates, the ascidian Ciona intestinalis (Vandenberghe et al 2001) and the appendiculariam Oikopleura dioica (Ganot et al 2004). It is absent in a variety of organisms where EST libraries were intensively sequenced, e.g.…”

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Pre-mRNA trans-splicing: from kinetoplastids to mammals, an easy language for life diversity

Mayer

Flöeter-Winter²

2005

Mem. Inst. Oswaldo Cruz

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Since the discovery that genes are split into intron and exons, the studies of the mechanisms involved in splicing pointed to presence of consensus signals in an attempt to generalize the process for all living cells. However, as discussed in the present review, splicing is a theme full of variations. The trans-splicing of pre-mRNAs, the joining of exons from distinct transcripts, is one of these variations with broad distribution in the phylogenetic tree. The biological meaning of this phenomenon is discussed encompassing reactions resembling a possible noise to mechanisms of gene expression regulation. All of them however, can contribute to the generation of life diversity.Key words: RNA processing -alternative trans-splicing -spliced leader RNA -trypanosomatids -nematodes -mammalian Most of the protein-coding eukaryotic genes display an interrupted structure alternating exons and introns. After transcription, introns must be removed from the primary transcript (pre-mRNA) to generate a translatable mature mRNA. It is interesting to note that the mature mRNA is constituted of 5' and 3' untranslatable regions (UTR) flanking the open reading frame (ORF) and that UTR are also exons. The precise excision of the introns and the joining of neighboring exons is a complex process generally named splicing, and when this processing occurs within a single pre-mRNA molecule it can also be called cis-splicing (Moore et al. 1993, Burge et al. 1999.Cis-splicing occurs in a two-step mechanism, each step consisting of a transesterification reaction (Moore et al. 1993) (Fig. 1A). The spliceosome, a ribonucleoprotein machinery composed of five small ribonucleoproteins (U1, U2, U4, U5, U6 snRNPs, named in relation to the kind of associated RNA molecule) and approximately 300 distinct proteins, is responsible for the splicing catalysis (Burge et al. 1999).Much effort was expended on the comprehension of the structure and dynamics of this complex machine during the splicing process, but the rules that discriminate introns and exons within the message are still poorly understood. Nevertheless, four conserved pre-mRNA sequence elements, which interact with the spliceosome, have been characterized as determinants in the splicing process (Moore et al. 1993, Burge et al. 1999 (Fig. 1C). In mammals, the 5' splice site consensus is AG/GURAGU (R for purine, /for splice site, bold for the dinucleotide 5' intron boundary) while the 3' splice site consensus is YAG/G (Y for pyrimidine, /for splice site, bold for the dinucleotides 3' intron boundary). There is also a conservation of nucleotide sequence around the branch point, CURAY (Y for pyrimidine, R for purine and A for branch Recently, other cis-regulatory elements were implicated in splice site recognition, e.g. the exonic splicing enhancers (ESEs) (Fig. 1C). ESEs are localized within exons and interact with a family of proteins rich in serine and arginine (SR proteins) that recruits the spliceosome to the proximal splice site .Although the presence of those consensuses was observed, it i...

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mRNA 5′-leader trans-splicing in the chordates

Cited by 138 publications

References 52 publications

Trans-spliced leader addition to mRNAs in a cnidarian

Trans-spliced leader addition to mRNAs in a cnidarian

A global analysis of C. elegans trans-splicing

Pre-mRNA trans-splicing: from kinetoplastids to mammals, an easy language for life diversity

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