Messenger RNAs with large numbers of upstream open reading frames are translated via leaky scanning and reinitiation in the asexual stages of Plasmodium falciparum
| Autor: | Chhaminder Kaur, Swati Patankar, Mayank Kumar |
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| Rok vydání: | 2020 |
| Předmět: |
Erythrocytes
Kozak consensus sequence Plasmodium falciparum Leaky scanning Protein Sorting Signals Biology Open Reading Frames 03 medical and health sciences 0302 clinical medicine Eukaryotic translation Humans RNA Messenger Gene 030304 developmental biology Genetics 0303 health sciences Translation (biology) Stop codon Open reading frame Infectious Diseases Genes Codon usage bias Animal Science and Zoology Parasitology RNA Protozoan 030217 neurology & neurosurgery Research Article |
| Zdroj: | Parasitology |
| ISSN: | 1469-8161 0031-1820 |
| DOI: | 10.1017/s0031182020000840 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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