Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.

The genome of Trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. In terms of regulation, the best-studied genes are procyclins, which encode a family of major surface GPI-anchored glycoproteins (EP1, EP2, EP3, GPEET) that show differential expression...

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Autores principales:	Pegine Walrad, Athina Paterou, Alvaro Acosta-Serrano, Keith R Matthews
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/09fafc9656da491ea70d701fbbfd7e77
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spelling	oai:doaj.org-article:09fafc9656da491ea70d701fbbfd7e772021-12-02T19:59:48ZDifferential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.1553-73661553-737410.1371/journal.ppat.1000317https://doaj.org/article/09fafc9656da491ea70d701fbbfd7e772009-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19247446/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The genome of Trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. In terms of regulation, the best-studied genes are procyclins, which encode a family of major surface GPI-anchored glycoproteins (EP1, EP2, EP3, GPEET) that show differential expression in the parasite's tsetse-fly vector. Although procyclin mRNA cis-regulatory sequences have provided the paradigm for post-transcriptional control in kinetoplastid parasites, trans-acting regulators of procyclin mRNAs are unidentified, despite intensive effort over 15 years. Here we identify the developmental regulator, TbZFP3, a CCCH-class predicted RNA binding protein, as an isoform-specific regulator of Procyclin surface coat expression in trypanosomes. We demonstrate (i) that endogenous TbZFP3 shows sequence-specific co-precipitation of EP1 and GPEET, but not EP2 and EP3, procyclin mRNA isoforms, (ii) that ectopic overexpression of TbZFP3 does not perturb the mRNA abundance of procyclin transcripts, but rather that (iii) their protein expression is regulated in an isoform-specific manner, as evidenced by mass spectrometric analysis of the Procyclin expression signature in the transgenic cell lines. The TbZFP3 mRNA-protein complex (TbZFP3mRNP) is identified as a trans-regulator of differential surface protein expression in trypanosomes. Moreover, its sequence-specific interactions with procyclin mRNAs are compatible with long-established predictions for Procyclin regulation. Combined with the known association of TbZFP3 with the translational apparatus, this study provides a long-sought missing link between surface protein cis-regulatory signals and the gene expression machinery in trypanosomes.Pegine WalradAthina PaterouAlvaro Acosta-SerranoKeith R MatthewsPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 2, p e1000317 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Pegine Walrad Athina Paterou Alvaro Acosta-Serrano Keith R Matthews Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.
description	The genome of Trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. In terms of regulation, the best-studied genes are procyclins, which encode a family of major surface GPI-anchored glycoproteins (EP1, EP2, EP3, GPEET) that show differential expression in the parasite's tsetse-fly vector. Although procyclin mRNA cis-regulatory sequences have provided the paradigm for post-transcriptional control in kinetoplastid parasites, trans-acting regulators of procyclin mRNAs are unidentified, despite intensive effort over 15 years. Here we identify the developmental regulator, TbZFP3, a CCCH-class predicted RNA binding protein, as an isoform-specific regulator of Procyclin surface coat expression in trypanosomes. We demonstrate (i) that endogenous TbZFP3 shows sequence-specific co-precipitation of EP1 and GPEET, but not EP2 and EP3, procyclin mRNA isoforms, (ii) that ectopic overexpression of TbZFP3 does not perturb the mRNA abundance of procyclin transcripts, but rather that (iii) their protein expression is regulated in an isoform-specific manner, as evidenced by mass spectrometric analysis of the Procyclin expression signature in the transgenic cell lines. The TbZFP3 mRNA-protein complex (TbZFP3mRNP) is identified as a trans-regulator of differential surface protein expression in trypanosomes. Moreover, its sequence-specific interactions with procyclin mRNAs are compatible with long-established predictions for Procyclin regulation. Combined with the known association of TbZFP3 with the translational apparatus, this study provides a long-sought missing link between surface protein cis-regulatory signals and the gene expression machinery in trypanosomes.
format	article
author	Pegine Walrad Athina Paterou Alvaro Acosta-Serrano Keith R Matthews
author_facet	Pegine Walrad Athina Paterou Alvaro Acosta-Serrano Keith R Matthews
author_sort	Pegine Walrad
title	Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.
title_short	Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.
title_full	Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.
title_fullStr	Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.
title_full_unstemmed	Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.
title_sort	differential trypanosome surface coat regulation by a ccch protein that co-associates with procyclin mrna cis-elements.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/09fafc9656da491ea70d701fbbfd7e77
work_keys_str_mv	AT peginewalrad differentialtrypanosomesurfacecoatregulationbyaccchproteinthatcoassociateswithprocyclinmrnaciselements AT athinapaterou differentialtrypanosomesurfacecoatregulationbyaccchproteinthatcoassociateswithprocyclinmrnaciselements AT alvaroacostaserrano differentialtrypanosomesurfacecoatregulationbyaccchproteinthatcoassociateswithprocyclinmrnaciselements AT keithrmatthews differentialtrypanosomesurfacecoatregulationbyaccchproteinthatcoassociateswithprocyclinmrnaciselements
_version_	1718375702198222848

Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.

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