The 3′-untranslated regions from the Trypanosoma brucei phosphoglycerate kinase-encoding genes mediate developmental regulation

Blattner, Judith; Clayton, Christine

doi:10.1016/0378-1119(95)00366-e

Cited by 51 publications

(38 citation statements)

References 27 publications

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“…In contrast, the rapid degradation of various highly unstable reporter mRNAs was initiated by destruction of the 39 end (Irmer and Clayton 2001), and exosome depletion delayed degradation (Haile et al 2003). The abundances of the CAT-EP, AAT11, PGKB, and PGKC transcripts are controlled by sequences in their 39 UTRs, which affect degradation, not processing (Hug et al 1993;Blattner and Clayton 1995;Quijada et al 2002;A. Robles and C. Colasante, unpubl.…”

Section: Discussionmentioning

confidence: 99%

Roles of aTrypanosoma brucei5′→3′ exoribonuclease homolog in mRNA degradation

Irmer²,

Gudjonsdottir-Planck³

et al. 2006

RNA

100

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The genome of the kinetoplastid parasite Trypanosoma brucei encodes four homologs of the Saccharomyces cerevisiae 59/39 exoribonucleases Xrn1p and Xrn2p/Rat1p, XRNA, XRNB, XRNC, and XRND. In S. cerevisiae, Xrn1p is a cytosolic enzyme involved in degradation of mRNA, whereas Xrn2p is involved in RNA processing in the nucleus. Trypanosome XRND was found in the nucleus, XRNB and XRNC were found in the cytoplasm, and XRNA appeared to be in both compartments. XRND and XRNA were essential for parasite growth. Depletion of XRNA increased the abundances of highly unstable developmentally regulated mRNAs, perhaps by delaying a deadenylation-independent decay pathway. Degradation of more stable or unregulated mRNAs was not affected by XRNA depletion although a slight decrease in average poly(A) tail length was observed. We conclude that in trypanosomes 59/39 exonuclease activity is important in degradation of highly unstable, regulated mRNAs, but that for other mRNAs another step is more important in determining the decay rate.

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Section: Discussionmentioning

confidence: 99%

Roles of aTrypanosoma brucei5′→3′ exoribonuclease homolog in mRNA degradation

Irmer²,

Gudjonsdottir-Planck³

et al. 2006

RNA

100

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“…Specifically, exosome subunits, in conjunction with cofactors, are important for the decay of the AU-rich element (ARE) containing c-fos and tumor necrosis factor (TNF) mRNAs (Chen et al 2001). Exosome subunits have also been linked to the surveillance of other UTR elements, as evidenced by the phosphoglycerate kinase mRNA (Blattner and Clayton 1995;Colasante et al 2007). Despite great progress in understanding the nature and scope of the RNA metabolic pathways and functions of individual exosome subunits, we are only beginning to comprehend how these subunits assemble and function as active complexes in vivo.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis reveals distinct substrate specificities of Rrp6, Dis3, and core exosome subunits

Kiss

Andrulis

2010

RNA

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The RNA processing exosome complex was originally defined as an evolutionarily conserved multisubunit complex of ribonucleases responsible for the processing and/or turnover of stable RNAs. The exosome complex is also involved in the surveillance of mRNAs in both the nucleus and the cytoplasm, including nonsense-mediated decay (NMD) targets. The detailed mechanisms for how individual exosome subunits participate in each of these RNA metabolic pathways remains unclear. Here, we use RNAi to deplete exosome subunits, the exonucleases Rrp6 and Dis3, and an exosome cofactor in Drosophila melanogaster S2 tissue culture cells and assay the effects on global mRNA levels using gene expression microarrays. Consistent with the RNA degradative activities ascribed to the exosome, most mRNAs are increased. Notably, these stabilized mRNAs possess 39 untranslated regions that are longer than the representative transcriptomic average. Moreover, our results reveal substantial differences in the pools of affected mRNAs for each depleted subunit. For example, ;25% of the affected transcripts in Rrp6 depleted cells represent NMD substrates. While the affected mRNAs were dissimilar, they encode proteins that function in similar cellular pathways. We conclude that individual exosome subunits are largely functionally independent at the transcript level, but are interdependent on a transcriptomic level.

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“…3). The presence of a regulatory cis-acting element in the 3 0 UTR of a differentially expressed mRNA has been reported for several other differentially expressed mRNAs in T. brucei (Hotz et al 1995;Hug et al 1993;Blattner and Clayton 1995;Furger et al 1997;Schürch et al 1997;Quijada et al 2002), as well as in T. cruzi (Coughlin et al 2000) and Leishmania spp. (Ramamoorthy et al 1995;Charest et al 1996;Kelly et al 2001).…”

Section: Discussionmentioning

confidence: 86%

“…Two life cycle stages of Trypanosoma brucei are readily cultured and manipulated in the laboratory, the mammalian bloodstream form and the insect procyclic form. The majority of differential gene expression in these two forms arises from developmentally regulated instability of individual mRNA species (Hug et al 1993;Blattner and Clayton 1995;Hotz et al 1995;Webb et al 2005). To date, no short cis-acting element that is necessary and sufficient for developmental regulation of mRNA stability has been identified in trypanosomes.…”

Section: Introductionmentioning

confidence: 99%

“…To date, no short cis-acting element that is necessary and sufficient for developmental regulation of mRNA stability has been identified in trypanosomes. Several mRNAs have been studied to identify cis-acting elements involved in developmentally regulated mRNA stability, and most work has concentrated on the characterization of elements from 3 0 UTRs that produce an effect on reporter gene expression (Hug et al 1993;Blattner and Clayton 1995;Hotz et al 1995;Quijada et al 2002). The work has identified U-rich elements that shorten mRNA half-life in bloodstream forms (Hotz et al 1997;Quijada et al 2002), but it is not clear whether these account for the full degree of differential expression observed for the native mRNA.…”

Section: Introductionmentioning

confidence: 99%

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A novel strategy to identify the location of necessary and sufficient cis-acting regulatory mRNA elements in trypanosomes

Webb

Burns²,

Kimblin³

et al. 2005

RNA

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Expression of nearly all protein coding genes in trypanosomes is regulated post-transcriptionally, predominantly at the level of mRNA half-life. The identification of cis-acting elements involved in mRNA stability has been hindered by a lack of ability to screen for loss-of-regulation mutants. The method described in this article allows the region containing the necessary and sufficient elements within a mRNA to be identified and uses antibiotic resistance genes as both selectable markers and reporters. In the case of unstable mRNAs, the strategy can be extended by performing a screen for spontaneous loss-of-function mutants in regulatory parts of a mRNA. The method was validated by using the GPI-PLC mRNA, which is unstable in procyclic form trypanosomes and showed that the 3 0 UTR of the GPI-PLC mRNA contains all elements required for developmentally regulated instability. Loss-of-instability mutants all contained deletions within the 2300-nucleotide-long 3 0 UTR, and their analysis showed that a deletion including the last 800 nt of the gene stabilized the mRNA. The method is nonpresumptive, allows far more rapid screening for cis-elements than existing procedures, and has the advantage of identifying functional mutants. It is applicable to all eukaryotes using polycistronic transcription.

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The 3′-untranslated regions from the Trypanosoma brucei phosphoglycerate kinase-encoding genes mediate developmental regulation

Cited by 51 publications

References 27 publications

Roles of aTrypanosoma brucei5′→3′ exoribonuclease homolog in mRNA degradation

Roles of aTrypanosoma brucei5′→3′ exoribonuclease homolog in mRNA degradation

Genome-wide analysis reveals distinct substrate specificities of Rrp6, Dis3, and core exosome subunits

A novel strategy to identify the location of necessary and sufficient cis-acting regulatory mRNA elements in trypanosomes

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