Identification of a small rna containing the trypanosome spliced leader: A donor of shared 5′ sequences of trypanosomatid mRNAs?

Milhausen, Michael; Nelson, Richard G.; Sather, Susan; Selkirk, Murray E.; Agabian, Nina

doi:10.1016/0092-8674(84)90267-8

Cited by 170 publications

(114 citation statements)

References 37 publications

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“…Whereas the first interpretation is far-fetched, the second is in full agreement with the results of the analysis of stable and nascent transcripts of miniexon genes and the DNA repeats in which they are embedded (Kooter et al, 1984;Campbell et al, 1984;Milhausen et al, 1984). The mini-exon has been found in the genome of several species of trypanosomes (De Lange et al, 1983Milhausen et al, 1984;Nelson et al, 1984). Hence, we conclude that transcription of VSG genes and possibly all proteincoding genes in Kinetoplastida is discontinuous.…”

Section: Introductionsupporting

confidence: 75%

Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.

Guyaux¹,

Cornelissen²,

Pays³

et al. 1985

The EMBO Journal

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Communicated by M.SteinertThe mRNAs for variant surface glycoproteins (VSGs) and many other proteins in Trypanosoma brucei start with the same sequence of 35 nucleotides, encoded by a separate miniexon. There are -200 mini-exon genes per trypanosome and these are highly clustered on large chromosomes. We have found two trypanosome variants that express a VSG gene located on a small, 225-kb chromosome. Each gene yields a mRNA containing the 35-nucleotide sequence even though the 225-kb chromosome does not contain a complete mini-exon gene. These results provide a strong support for the hypothesis that transcription of protein-coding genes in trypanosomes is discontinuous.

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Section: Introductionsupporting

confidence: 75%

Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.

Guyaux¹,

Cornelissen²,

Pays³

et al. 1985

The EMBO Journal

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“…Most of the differences were 1 or 2 bp insertions or deletions, which particularly occured in non-transcribed homopolymer tracts. Similar levels of mismatch occur between 1.4 kb elements isolated from a given cloned cell line or between different T. brucei stocks (11,13,24,25).…”

Section: Resultsmentioning

confidence: 73%

“…Orphons have since been found in gene families as diverse as the 5S and tRNA genes of Xenopus laevis (2), a major tandem repeat family from the human X chromosome (with dispersed members on autosomes) (3), and genes encoding the rRNAs of yeast (1). Both RNA and DNA mediated mechanisms of gene dispersal have been proposed to account for the (11)(12)(13). The vast majority of the 100 to 200 1.4 kb units are directly and tandemly repeated in the genome, but a few are orphons (6).…”

Section: Introductionmentioning

confidence: 99%

The trypanosome spliced leader small RNA gene family: stage-specific modification of one of several similar dispersed genes

Parsons¹,

Nelson²,

Agabian³

1986

Nucl Acids Res

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Diverse mRNAs of Trypanosoma brucei possess the same 5' terminal 35 nucleotides, termed the spliced leader (SL), which appears to be derived from a separate 135 nucleotide transcript. This small SL RNA is encoded within a 1.4 kb unit of DNA which is tandemly reiterated in the genome. In addition, there are at least 4 orphon elements containing SL sequences dispersed from the tandem array. Here we show that during the trypanosome life cycle one of the SL orphons undergoes a stage-specific modification that prevents cleavage of an EcoRV site and we further demonstrate that although only one orphon is modified, three of the SL orphons are flanked by very similar sequences. Each of these contains SL reiteration units including the non-transcribed spacer DNA, suggesting that they did not originate through an RNA intermediate. In addition no evidence of direct repeats at the junction of 1.4 kb and non-1.4 kb DNA was observed. Finally, a phylogenetic survey indicates that while many trypanosomatid species possess similarly organized SL-like sequences, only the SL orphons of closely related subspecies of the T. brucei -T. evansi complex share similar flanking regions.

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“…Expression studies showed that transcription of the leader sequences generates a small RNA of 135-147 nt, which contains the 39 nt leader sequence at its 5' termini (Milhausen et al 1984). Although these results exclude the occurrence of cis-splicing, other hypotheses were proposed to explain the structure of mature mRNAs of trypanosomes: (i) the pre-mRNA is transcribed using the leader sequence as initiator, and the resulting molecule is then processed by cis-splicing; (ii) the independently transcribed short RNA bearing the leader sequence is ligated, via its 3' end to the 5' end of the pre-mRNA and the resulting molecule is spliced in cis; (iii) the leader RNA and the pre-mRNA could be independently transcribed as in (ii) but the two substrates could be spliced in trans.…”

mentioning

confidence: 99%

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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Identification of a small rna containing the trypanosome spliced leader: A donor of shared 5′ sequences of trypanosomatid mRNAs?

Cited by 170 publications

References 37 publications

Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.

Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.

The trypanosome spliced leader small RNA gene family: stage-specific modification of one of several similar dispersed genes

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

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