Mechanisms of developmental regulation in Trypanosoma brucei: a polypyrimidine tract in the 3'-untranslated region of a surface protein mRNA affects RNA abundance and translation

Hotz, Hans-Rudolf; Hartmann, Claudia; Huober, Karin; Hug, Michael; Clayton, Christine

doi:10.1093/nar/25.15.3017

Cited by 124 publications

(99 citation statements)

References 52 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We anticipate that a common translational or posttranslational mechanism may coordinately up-regulate citric acid cycle activities upon differentiation. Whereas numerous examples suggest a predominance of regulation at the level of differential mRNA stability in trypanosomatids (101,102), only a handful of examples of translational or post-translational regulation have been reported (103)(104)(105)(106)(107). …”

Section: Figmentioning

confidence: 99%

A Developmentally Regulated Aconitase Related to Iron-regulatory Protein-1 Is Localized in the Cytoplasm and in the Mitochondrion of Trypanosoma brucei

Saas¹,

Ziegelbauer²,

Haeseler³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Figmentioning

confidence: 99%

A Developmentally Regulated Aconitase Related to Iron-regulatory Protein-1 Is Localized in the Cytoplasm and in the Mitochondrion of Trypanosoma brucei

Saas¹,

Ziegelbauer²,

Haeseler³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…These elements have been identified in T. brucei procyclin mRNA as 16-mer stem-loop and 26-mer polypyrimidine tract sequences in the 3Ј-UTR, which, upon interaction with certain proteins, promote stabilization and translation of the target RNA, respectively (12,13). In T. cruzi, the stability of mRNA coding for reporter genes is also modulated by the 3Ј-UTR of some members of the 85-kDa glycoprotein family (6).…”

Section: Figmentioning

confidence: 99%

“…During processing, capped spliced leader sequence is added to the 5Ј-end, and a polyadenosine tail is added to the 3Ј-end of mRNA (10), probably ensuring mRNA stability and transport to the cytoplasm (11). In particular, correct splicing and polyadenylation, as well as the existence of specific 3Ј-untranslated portions of the transcribed genes, have been shown to promote either mRNA stability (12) or an increase in the translational efficiency (13). However, the nature of controlling factors and how environmental modifications induce differential expression remain obscure.…”

mentioning

confidence: 99%

Expression of trans-Sialidase and 85-kDa Glycoprotein Genes in Trypanosoma cruzi Is Differentially Regulated at the Post-transcriptional Level by Labile Protein Factors

Abuin¹,

Freitas‐Junior²,

Colli³

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

To adapt to different environments, Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, expresses a different set of proteins during development. To begin to understand the mechanism that controls this differential gene expression, we have analyzed the levels of amastin and trans-sialidase mRNAs and the mRNAs encoding members of the 85-kDa glycoprotein gene family, which are differentially expressed in the T. cruzi stages found in the mammalian host. Amastin mRNA is expressed predominantly in intracellular and proliferative amastigotes. trans-Sialidase mRNAs are found mostly in forms undergoing transformation from amastigotes to trypomastigotes inside infected cells, whereas mRNAs encoding the 85-kDa glycoproteins appear only in the infective trypomastigotes released from the cells. The genes coding for these mRNA species are constitutively transcribed in all stages of T. cruzi cells, suggesting that expression is controlled post-transcriptionally during differentiation. Inhibition of transcription by actinomycin D revealed that each mRNA species has a relatively long half-life in stages where it accumulates. In the case of the transsialidase and 85-kDa glycoprotein genes, mRNA accumulation was induced by treatment with the protein synthesis inhibitor cycloheximide at the stages that preceded the normal accumulation. Therefore, mRNA stabilization may account for mRNA accumulation. mRNA degradation could be promoted by proteins with high turnover, or stabilization could be promoted by forming a complex with the translational machinery at defined times in development. Identification of the factors that induce mRNA degradation or stabilization is essential to the understanding of control of gene expression in these organisms.Gene expression in Trypanosoma cruzi as well as in other trypanosomes is largely controlled at the post-transcriptional level (1-6), although there are a few exceptions where promoters and transcriptional activation have been described (7). Well defined RNA polymerase II initiation sites have not been found, and most genes are transcribed as part of polycistronic units and are processed by trans-splicing (8, 9). During processing, capped spliced leader sequence is added to the 5Ј-end, and a polyadenosine tail is added to the 3Ј-end of mRNA (10), probably ensuring mRNA stability and transport to the cytoplasm (11). In particular, correct splicing and polyadenylation, as well as the existence of specific 3Ј-untranslated portions of the transcribed genes, have been shown to promote either mRNA stability (12) or an increase in the translational efficiency (13). However, the nature of controlling factors and how environmental modifications induce differential expression remain obscure.T. cruzi provides an attractive model to study how modifications in the environment induce differential gene expression. In the insect host, the epimastigote form of the parasite proliferates in the gut. In the posterior gut, where the nutrients become scarce, the parasite transforms into metacyclic ...

show abstract

“…PRO mRNA is much more abundant in PCF cells than BSF cells [12]. Using unique restriction sites within the pMP plasmid, the PRO 5′-UTR was replaced with either a VSG-specific or ACT-specific 5′-UTR sequence (Fig.…”

mentioning

confidence: 99%

Different trans RNA splicing events in bloodstream and procyclic Trypanosoma brucei

Helm

Wilson

Donelson

2008

Molecular and Biochemical Parasitology

View full text Add to dashboard Cite

A distinctive feature of Trypanosoma brucei and other trypanosomatids is that most of their genes are transcribed into long polycistronic RNAs [1], which are processed into mature monocistronic mRNAs bearing a 39-nucleotide spliced leader (SL) at their 5′ ends that is derived from a capped precursor RNA of ∼140 nucleotides [2;3]. This trans RNA splicing serves two major functions: in conjunction with 3′ polyadenylation it generates the mature mRNAs from polycistronic primary transcripts, and via the SL it provides a 5′ cap structure for each mRNA [1;4]. In contrast to cis RNA splicing of introns in other eukaryotes, trans RNA splicing unites exons from two independently transcribed RNAs. trans and cis RNA splicing, however, share several similarities. For example, at least some components of the cis RNA spliceosomes are conserved in T. brucei, and both cis and trans RNA splicing utilize the same general mechanism and require the same general sequence motifs [4]. During an examination of the effect of different 3′ UTRs on gene expression in T. brucei, we noticed differences between bloodstream form (BSF) and procyclic form (PCF) trypanosomes in the addition of SLs to RNAs transcribed from a luciferase reporter gene inserted into the rRNA gene locus. Further inspection revealed that in PCF cells the expected SL addition occurs to precursor luciferase RNA, whereas in BSF cells multiple SL additions occur to the same luciferase RNA that are independent of the 5′ and 3′ UTR sequences. Fig. 1A depicts the luciferase reporter plasmid, pMP, integrated into the rRNA gene spacer region of the T. brucei genome that was used for the experiments. This plasmid is derived from plasmid pHD496 (kindly provided by C. Clayton), and is used to measure luciferase activity in BSF and PCF cells when various 3′-UTRs are inserted at a BamHI site directly behind the luciferase coding sequence (LUC). An initial northern blot of RNA from BSF cells bearing integrated pMP revealed the presence of multiple RNA species recognized by a LUC probe (Fig 1B). The three bands indicated by arrowheads coincide with the locations of rRNAs and are likely due to entrapment of some luciferase RNA in these rRNAs. The RNA bands indicated by L (long), LUC and S (short) were examined further. To look for potential differential luciferase expression from the same inserted plasmid in BSF and PCF cells of the same * Corresponding author. Tel.: +1-319-335-7934; fax: +1-319-335-9570, Email address: E-mail: john-donelson@uiowa.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH...

show abstract

Mechanisms of developmental regulation in Trypanosoma brucei: a polypyrimidine tract in the 3'-untranslated region of a surface protein mRNA affects RNA abundance and translation

Cited by 124 publications

References 52 publications

A Developmentally Regulated Aconitase Related to Iron-regulatory Protein-1 Is Localized in the Cytoplasm and in the Mitochondrion of Trypanosoma brucei

A Developmentally Regulated Aconitase Related to Iron-regulatory Protein-1 Is Localized in the Cytoplasm and in the Mitochondrion of Trypanosoma brucei

Expression of trans-Sialidase and 85-kDa Glycoprotein Genes in Trypanosoma cruzi Is Differentially Regulated at the Post-transcriptional Level by Labile Protein Factors

Different trans RNA splicing events in bloodstream and procyclic Trypanosoma brucei

Contact Info

Product

Resources

About