A new developmentally regulated gene family in Leishmania amastigotes encoding a homolog of amastin surface proteins

Wu, Ying; Fakhry, Youssef El; Sereno, Denis; Tamar, Samira; Papadopoulou, Barbara

doi:10.1016/s0166-6851(00)00290-5

Cited by 98 publications

(110 citation statements)

References 44 publications

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“…A number of workers have carried out methods searching for changes in gene expression amongst Leishmania stages, using methods such as differential or subtractive hybridization and differential display (Coulson & Smith 1990;Charest & Matlashewski 1994;Pogue et al 1995;Heard et al 1996;Liu et al 2000;Wu et al 2000). While a number of genes showing significant regulation by transcript abundance were found, most workers remarked that they were able to identify only a relatively small number of differentially regulated genes, in agreement with our preliminary microarray results.…”

Section: Mrna-expression Profiling: a Genome-wide Survey Of Leishmanisupporting

confidence: 81%

Putting theLeishmaniagenome to work: functional genomics by transposon trapping and expression profiling

Beverley

Akopyants

Goyard

et al. 2002

Phil. Trans. R. Soc. Lond. B

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Leishmania are important protozoan pathogens of humans in temperate and tropical regions. The study of gene expression during the infectious cycle, in mutants or after environmental or chemical stimuli, is a powerful approach towards understanding parasite virulence and the development of control measures. Like other trypanosomatids, Leishmania gene expression is mediated by a polycistronic transcriptional process that places increased emphasis on post-transcriptional regulatory mechanisms including RNA processing and protein translation. With the impending completion of the Leishmania genome, global approaches surveying mRNA and protein expression are now feasible. Our laboratory has developed the Drosophila transposon mariner as a tool for trapping Leishmania genes and studying their regulation in the form of protein fusions; a classic approach in other microbes that can be termed 'proteogenomics'. Similarly, we have developed reagents and approaches for the creation of DNA microarrays, which permit the measurement of RNA abundance across the parasite genome. Progress in these areas promises to greatly increase our understanding of global mechanisms of gene regulation at both mRNA and protein levels, and to lead to the identification of many candidate genes involved in virulence.

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Section: Mrna-expression Profiling: a Genome-wide Survey Of Leishmanisupporting

confidence: 81%

Putting theLeishmaniagenome to work: functional genomics by transposon trapping and expression profiling

Beverley

Akopyants

Goyard

et al. 2002

Phil. Trans. R. Soc. Lond. B

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“…Mature mRNAs are subsequently obtained from coordinated polyadenylation and trans-splicing, which adds a 39-nt spliced leader (SL) sequence to the 5' end of all mRNAs [30,31]. As a consequence of this unusual gene organization, Leishmania gene expression appears to not be regulated at the level of transcription [32], but stage-specific expression of a number of genes has been shown to be regulated via mRNA stability [8,[33][34][35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Saxena

Lahav

Holland

et al. 2007

Molecular and Biochemical Parasitology

147

137

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Leishmania donovani is an intracellular protozoan parasite that causes kala-azar in humans. During infection the extracellular insect forms (promastigotes) undergo rapid differentiation to intracellular amastigotes that proliferates in phagolysosomes of mammalian macrophages. We used microarraybased expression profiling to investigate the time-course of changes in RNA abundance during promastigote-to-amastigote differentiation in a host-free system that mimics this process. These studies revealed that several hundred genes underwent an ordered progression of transient or permanent up-and down-regulation during differentiation. Genes that were permanently upregulated in amastigotes were enriched for transporters and surface proteins, but under-represented in genes involved in protein and other metabolism. Most of these changes occurred late in the differentiation process, when morphological differentiation was essentially complete. Downregulated genes were over-represented in those involved in cell motility, growth and/or maintenance, and these changes generally occurred earlier in the process. Genes that were transiently up-or downregulated during differentiation included those encoding heat shock proteins, ubiquitin hydrolases, RNA binding proteins, protein kinases, a protein phosphatase, and a histone deacetylase. These results suggest that changes in mRNA abundance may be important in signal transduction, as well as protein and mRNA turnover, during differentiation. In addition to these mRNA changes, other transcripts including one or more rRNAs and snoRNAs, and non-coding RNAs from several telomeres, also showed substantial changes in abundance during the differentiation process. This paper provides the first genome-scale quantitative analysis of gene expression during the transition from promastigotes to amastigotes and demonstrates the utility of the host-free differentiation system.

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“…Quite useful for gene function studies are the reporter genes, e.g. luciferase or GFP (green fluorescent protein), which are applicable to studying regulatory elements involved in mRNA stability or initiation of translation control [89][90][91] and to evaluate protein interactions or subcellular distribution.…”

Section: Forward and Reverse Geneticsmentioning

confidence: 99%

Using Genomic Information to Understand Leishmania Biology

Toledo¹

2010

TOPARAJ

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Abstract:The genomes of different species of Leishmania have been deciphered in recent years. We learned that the genome content and organization of Leishmania major, Leishmania braziliensis and Leishmania infantum are highly similar and annotation of these genomes revealed that there are few species-specific genes. Association of genome information with reverse and forward genetics approaches allows posing and answering relevant biological questions in a novel way. In this article we briefly present an overview of relevant aspects of genome organization of the Leishmania and how this information can be used to improve our understanding of the biology, pathogenesis, host-parasite interaction issues. We present some of the most useful bioinformatics tools/softwares, which are currently available and how each one of them can be used to explore the genome supporting a wide variety of queries. We included other computational tools which allow integrating the genome data with biochemical pathways revealing metabolic and regulatory networks to be investigated. Finally, we discuss reverse and forward genetic tools available and finalize with considerations on established and novel high-throughput approaches at the genome, transcriptome and proteome levels.

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A new developmentally regulated gene family in Leishmania amastigotes encoding a homolog of amastin surface proteins

Cited by 98 publications

References 44 publications

Putting theLeishmaniagenome to work: functional genomics by transposon trapping and expression profiling

Putting theLeishmaniagenome to work: functional genomics by transposon trapping and expression profiling

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Using Genomic Information to Understand Leishmania Biology

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