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In silico and biological survey of transcription-associated proteins implicated in the transcriptional machinery during the erythrocytic development of Plasmodium falciparum.

Bischoff E, Vaquero C - BMC Genomics (2010)

Bottom Line: The transcription-associated proteins were clustered in three main sets of factors: general transcription factors, chromatin-related proteins (structuring, remodelling and histone modifying enzymes), and specific transcription factors.This is the first attempt to build a comprehensive directory of potential transcription-associated proteins in Plasmodium.In addition, all complete transcriptome, proteome and interactome raw data were re-analysed, compared and discussed for a better comprehension of the complex biological processes of Plasmodium falciparum transcriptional regulation during the erythrocytic development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, 25-28 rue du Dr Roux, 75724, Paris cedex 15, France. bischoff@pasteur.fr

ABSTRACT

Background: Malaria is the most important parasitic disease in the world with approximately two million people dying every year, mostly due to Plasmodium falciparum infection. During its complex life cycle in the Anopheles vector and human host, the parasite requires the coordinated and modulated expression of diverse sets of genes involved in epigenetic, transcriptional and post-transcriptional regulation. However, despite the availability of the complete sequence of the Plasmodium falciparum genome, we are still quite ignorant about Plasmodium mechanisms of transcriptional gene regulation. This is due to the poor prediction of nuclear proteins, cognate DNA motifs and structures involved in transcription.

Results: A comprehensive directory of proteins reported to be potentially involved in Plasmodium transcriptional machinery was built from all in silico reports and databanks. The transcription-associated proteins were clustered in three main sets of factors: general transcription factors, chromatin-related proteins (structuring, remodelling and histone modifying enzymes), and specific transcription factors. Only a few of these factors have been molecularly analysed. Furthermore, from transcriptome and proteome data we modelled expression patterns of transcripts and corresponding proteins during the intra-erythrocytic cycle. Finally, an interactome of these proteins based either on in silico or on 2-yeast-hybrid experimental approaches is discussed.

Conclusion: This is the first attempt to build a comprehensive directory of potential transcription-associated proteins in Plasmodium. In addition, all complete transcriptome, proteome and interactome raw data were re-analysed, compared and discussed for a better comprehension of the complex biological processes of Plasmodium falciparum transcriptional regulation during the erythrocytic development.

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Comparison of transcriptome and proteome data issued from Winzeler's, Florens' and Lasonder's reports. Winzeler's transcriptome data, obtained from two different culture synchronizations (see Figure 1), was ordered according to the I-IV class of TAPs and compared to the proteome data obtained from A, B, C and D reports (from left to right) [29-32]. The colorimetric representation of the transcriptome is as in figure 1. The colorimetric representation for the proteome is black-blue for low, orange-red for high as indicated on top of figure. Grey represents absence of detection. Details for each TAP are as in the previous figures.
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Figure 3: Comparison of transcriptome and proteome data issued from Winzeler's, Florens' and Lasonder's reports. Winzeler's transcriptome data, obtained from two different culture synchronizations (see Figure 1), was ordered according to the I-IV class of TAPs and compared to the proteome data obtained from A, B, C and D reports (from left to right) [29-32]. The colorimetric representation of the transcriptome is as in figure 1. The colorimetric representation for the proteome is black-blue for low, orange-red for high as indicated on top of figure. Grey represents absence of detection. Details for each TAP are as in the previous figures.

Mentions: The proteome data are based on four different reports [29-32] that, for simplification, we will refer to in the following paragraph as A, B, C and D for Le Roch, Florens and the two Lasonder's reports. Figure 3 shows on the left, the A transcriptome data with respect to every class of TAP from I to IV and seven different parasite stages of erythrocytic development as well as gametocytes and sporozoites (indicated top of the figure) for comparison with their cognate proteins. For A and B proteome reports, the same methodology was used based on MudPIT followed by mass spectrometry. The A data reported the identification of 130 TAP of the 202 listed in the directory (Table 1) and B data 114. Most of the factors were identified by both groups, while a few of them were identified only by C. The methodology used by C and D was based on 1D gel protein fractionation of mainly the gametocyte stages and parasite stages from the mosquito followed by MS. They reported only 47 TAP including several additional proteins not detected by either group A or B. It is noteworthy that the total number of proteins determined by the A, B and C groups (139 proteins, including the six additional of C) throughout erythrocytic development represents around half the number of transcripts. It has been already stated that the number of identified proteins is markedly lower than that of transcripts most probably due to the different sensitivity of the experimental approaches. Indeed, the global analysis in Plasmodium described 4294 transcripts with only 2904 cognate proteins detected in the investigated erythrocytic stages [29].


In silico and biological survey of transcription-associated proteins implicated in the transcriptional machinery during the erythrocytic development of Plasmodium falciparum.

Bischoff E, Vaquero C - BMC Genomics (2010)

Comparison of transcriptome and proteome data issued from Winzeler's, Florens' and Lasonder's reports. Winzeler's transcriptome data, obtained from two different culture synchronizations (see Figure 1), was ordered according to the I-IV class of TAPs and compared to the proteome data obtained from A, B, C and D reports (from left to right) [29-32]. The colorimetric representation of the transcriptome is as in figure 1. The colorimetric representation for the proteome is black-blue for low, orange-red for high as indicated on top of figure. Grey represents absence of detection. Details for each TAP are as in the previous figures.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821373&req=5

Figure 3: Comparison of transcriptome and proteome data issued from Winzeler's, Florens' and Lasonder's reports. Winzeler's transcriptome data, obtained from two different culture synchronizations (see Figure 1), was ordered according to the I-IV class of TAPs and compared to the proteome data obtained from A, B, C and D reports (from left to right) [29-32]. The colorimetric representation of the transcriptome is as in figure 1. The colorimetric representation for the proteome is black-blue for low, orange-red for high as indicated on top of figure. Grey represents absence of detection. Details for each TAP are as in the previous figures.
Mentions: The proteome data are based on four different reports [29-32] that, for simplification, we will refer to in the following paragraph as A, B, C and D for Le Roch, Florens and the two Lasonder's reports. Figure 3 shows on the left, the A transcriptome data with respect to every class of TAP from I to IV and seven different parasite stages of erythrocytic development as well as gametocytes and sporozoites (indicated top of the figure) for comparison with their cognate proteins. For A and B proteome reports, the same methodology was used based on MudPIT followed by mass spectrometry. The A data reported the identification of 130 TAP of the 202 listed in the directory (Table 1) and B data 114. Most of the factors were identified by both groups, while a few of them were identified only by C. The methodology used by C and D was based on 1D gel protein fractionation of mainly the gametocyte stages and parasite stages from the mosquito followed by MS. They reported only 47 TAP including several additional proteins not detected by either group A or B. It is noteworthy that the total number of proteins determined by the A, B and C groups (139 proteins, including the six additional of C) throughout erythrocytic development represents around half the number of transcripts. It has been already stated that the number of identified proteins is markedly lower than that of transcripts most probably due to the different sensitivity of the experimental approaches. Indeed, the global analysis in Plasmodium described 4294 transcripts with only 2904 cognate proteins detected in the investigated erythrocytic stages [29].

Bottom Line: The transcription-associated proteins were clustered in three main sets of factors: general transcription factors, chromatin-related proteins (structuring, remodelling and histone modifying enzymes), and specific transcription factors.This is the first attempt to build a comprehensive directory of potential transcription-associated proteins in Plasmodium.In addition, all complete transcriptome, proteome and interactome raw data were re-analysed, compared and discussed for a better comprehension of the complex biological processes of Plasmodium falciparum transcriptional regulation during the erythrocytic development.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, 25-28 rue du Dr Roux, 75724, Paris cedex 15, France. bischoff@pasteur.fr

ABSTRACT

Background: Malaria is the most important parasitic disease in the world with approximately two million people dying every year, mostly due to Plasmodium falciparum infection. During its complex life cycle in the Anopheles vector and human host, the parasite requires the coordinated and modulated expression of diverse sets of genes involved in epigenetic, transcriptional and post-transcriptional regulation. However, despite the availability of the complete sequence of the Plasmodium falciparum genome, we are still quite ignorant about Plasmodium mechanisms of transcriptional gene regulation. This is due to the poor prediction of nuclear proteins, cognate DNA motifs and structures involved in transcription.

Results: A comprehensive directory of proteins reported to be potentially involved in Plasmodium transcriptional machinery was built from all in silico reports and databanks. The transcription-associated proteins were clustered in three main sets of factors: general transcription factors, chromatin-related proteins (structuring, remodelling and histone modifying enzymes), and specific transcription factors. Only a few of these factors have been molecularly analysed. Furthermore, from transcriptome and proteome data we modelled expression patterns of transcripts and corresponding proteins during the intra-erythrocytic cycle. Finally, an interactome of these proteins based either on in silico or on 2-yeast-hybrid experimental approaches is discussed.

Conclusion: This is the first attempt to build a comprehensive directory of potential transcription-associated proteins in Plasmodium. In addition, all complete transcriptome, proteome and interactome raw data were re-analysed, compared and discussed for a better comprehension of the complex biological processes of Plasmodium falciparum transcriptional regulation during the erythrocytic development.

Show MeSH
Related in: MedlinePlus