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Messenger RNAs with large numbers of upstream open reading frames are translated via leaky scanning and reinitiation in the asexual stages of Plasmodium falciparum

Published online by Cambridge University Press:  26 May 2020

Chhaminder Kaur ,
Mayank Kumar  and
Swati Patankar Open the ORCID record for Swati Patankar [Opens in a new window]
Chhaminder Kaur
Affiliation:
Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
Mayank Kumar
Affiliation:
Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
Swati Patankar*
Affiliation:
Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
*
Author for correspondence: Swati Patankar, E-mail: patankar@iitb.ac.in
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Abstract

The genome of Plasmodium falciparum has one of the most skewed base-pair compositions of any eukaryote, with an AT content of 80–90%. As start and stop codons are AT-rich, the probability of finding upstream open reading frames (uORFs) in messenger RNAs (mRNAs) is high and parasite mRNAs have an average of 11 uORFs in their leader sequences. Similar to other eukaryotes, uORFs repress the translation of the downstream open reading frame (dORF) in P. falciparum, yet the parasite translation machinery is able to bypass these uORFs and reach the dORF to initiate translation. This can happen by leaky scanning and/or reinitiation.

In this report, we assessed leaky scanning and reinitiation by studying the effect of uORFs on the translation of a dORF, in this case, the luciferase reporter gene, and showed that both mechanisms are employed in the asexual blood stages of P. falciparum. Furthermore, in addition to the codon usage of the uORF, translation of the dORF is governed by the Kozak sequence and length of the uORF, and inter-cistronic distance between the uORF and dORF. Based on these features whole-genome data was analysed to uncover classes of genes that might be regulated by uORFs. This study indicates that leaky scanning and reinitiation appear to be widespread in asexual stages of P. falciparum, which may require modifications of existing factors that are involved in translation initiation in addition to novel, parasite-specific proteins.

Keywords

leaky scanningP. falciparumreinitiationtranslationupstream ORFs
Type
Research Article
Information
Parasitology , Volume 147 , Issue 10 , September 2020 , pp. 1100 - 1113
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

Current address: Amity Institute of Biotechnology, Amity University, Panvel, Maharashtra 410206, India.

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