A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.

Clonally variant protein expression in the malaria parasite Plasmodium falciparum generates phenotypic variability and allows isogenic populations to adapt to environmental changes encountered during blood stage infection. The underlying regulatory mechanisms are best studied for the major virulence...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nicolas M B Brancucci, Kathrin Witmer, Christoph Schmid, Till S Voss
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e6c2a9c9fc24425da696484299b14df8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e6c2a9c9fc24425da696484299b14df8
record_format	dspace
spelling	oai:doaj.org-article:e6c2a9c9fc24425da696484299b14df82021-11-18T08:15:18ZA var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.1932-620310.1371/journal.pone.0100183https://doaj.org/article/e6c2a9c9fc24425da696484299b14df82014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24937593/?tool=EBIhttps://doaj.org/toc/1932-6203Clonally variant protein expression in the malaria parasite Plasmodium falciparum generates phenotypic variability and allows isogenic populations to adapt to environmental changes encountered during blood stage infection. The underlying regulatory mechanisms are best studied for the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is encoded by the multicopy var gene family and only a single variant is expressed in individual parasites, a concept known as mutual exclusion or singular gene choice. var gene activation occurs in situ and is achieved through the escape of one locus from epigenetic silencing. Singular gene choice is controlled at the level of transcription initiation and var 5' upstream (ups) sequences harbour regulatory information essential for mutually exclusive transcription as well as for the trans-generational inheritance of the var activity profile. An additional level of control has recently been identified for the var2csa gene, where an mRNA element in the 5' untranslated region (5' UTR) is involved in the reversible inhibition of translation of var2csa transcripts. Here, we extend the knowledge on post-transcriptional var gene regulation to the common upsC type. We identified a 5' UTR sequence that inhibits translation of upsC-derived mRNAs. Importantly, this 5' UTR element efficiently inhibits translation even in the context of a heterologous upstream region. Further, we found var 5' UTRs to be significantly enriched in uAUGs which are known to impair the efficiency of protein translation in other eukaryotes. Our findings suggest that regulation at the post-transcriptional level is a common feature in the control of PfEMP1 expression in P. falciparum.Nicolas M B BrancucciKathrin WitmerChristoph SchmidTill S VossPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e100183 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicolas M B Brancucci Kathrin Witmer Christoph Schmid Till S Voss A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.
description	Clonally variant protein expression in the malaria parasite Plasmodium falciparum generates phenotypic variability and allows isogenic populations to adapt to environmental changes encountered during blood stage infection. The underlying regulatory mechanisms are best studied for the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is encoded by the multicopy var gene family and only a single variant is expressed in individual parasites, a concept known as mutual exclusion or singular gene choice. var gene activation occurs in situ and is achieved through the escape of one locus from epigenetic silencing. Singular gene choice is controlled at the level of transcription initiation and var 5' upstream (ups) sequences harbour regulatory information essential for mutually exclusive transcription as well as for the trans-generational inheritance of the var activity profile. An additional level of control has recently been identified for the var2csa gene, where an mRNA element in the 5' untranslated region (5' UTR) is involved in the reversible inhibition of translation of var2csa transcripts. Here, we extend the knowledge on post-transcriptional var gene regulation to the common upsC type. We identified a 5' UTR sequence that inhibits translation of upsC-derived mRNAs. Importantly, this 5' UTR element efficiently inhibits translation even in the context of a heterologous upstream region. Further, we found var 5' UTRs to be significantly enriched in uAUGs which are known to impair the efficiency of protein translation in other eukaryotes. Our findings suggest that regulation at the post-transcriptional level is a common feature in the control of PfEMP1 expression in P. falciparum.
format	article
author	Nicolas M B Brancucci Kathrin Witmer Christoph Schmid Till S Voss
author_facet	Nicolas M B Brancucci Kathrin Witmer Christoph Schmid Till S Voss
author_sort	Nicolas M B Brancucci
title	A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.
title_short	A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.
title_full	A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.
title_fullStr	A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.
title_full_unstemmed	A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.
title_sort	var gene upstream element controls protein synthesis at the level of translation initiation in plasmodium falciparum.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e6c2a9c9fc24425da696484299b14df8
work_keys_str_mv	AT nicolasmbbrancucci avargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT kathrinwitmer avargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT christophschmid avargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT tillsvoss avargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT nicolasmbbrancucci vargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT kathrinwitmer vargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT christophschmid vargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum AT tillsvoss vargeneupstreamelementcontrolsproteinsynthesisattheleveloftranslationinitiationinplasmodiumfalciparum
_version_	1718422018555117568

A var gene upstream element controls protein synthesis at the level of translation initiation in Plasmodium falciparum.

Ejemplares similares