An upstream open reading frame (uORF) signals for cellular localization of the virulence factor implicated in pregnancy associated malaria

Yair Fastman, Shany Assaraf, Miriam Rose, Elad Milrot, Katherine Basore, B. Sivanandam Arasu, Sanjay A. Desai, Michael Elbaum, Ron Dzikowski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Plasmodium falciparum, the causative agent of the deadliest form of human malaria, alternates expression of variable antigens, encoded by members of a multi-copy gene family named var. Invar2csa, thevar gene implicated in pregnancy-associated malaria, translational repression is regulated by a unique upstream open reading frame (uORF) found only in its 5' UTR. Here, we report that this translated uORF significantly alters both transcription and posttranslational protein trafficking. The parasite can alter a protein's destinationwithout anymodifications to the protein itself, but instead by an element within the 5' UTR of the transcript. This uORF-dependent localization was confirmed by single molecule STORM imaging, followed by fusion of the uORF to a reporter gene which changes its cellular localization from cytoplasmic to ER-associated. These data point towards a novel regulatory role of uORF in protein trafficking, with important implications for the pathology of pregnancy-associated malaria.

Original languageAmerican English
Pages (from-to)4919-4932
Number of pages14
JournalNucleic Acids Research
Volume46
Issue number10
DOIs
StatePublished - 1 Jun 2018

Bibliographical note

Publisher Copyright:
© The Author(s) 2018.

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