Evidence map›Paper›PMID 26692187›Full record

ArticleMalaria journal2015

Upstream AUGs and upstream ORFs can regulate the downstream ORF in Plasmodium falciparum.

Mayank Kumar, Vivek Srinivas, Swati Patankar

Open access · goldAbstract read
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Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 25 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Mayank KumarDepartment of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India. mayank86@iitb.ac.in.
Vivek SrinivasDepartment of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India. viveksrinivas@iitb.ac.in.
Swati PatankarDepartment of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India. patankar@iitb.ac.in.
Indian Institute of Technology Bombay · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUpstream open reading frames (uORFs) and upstream AUGs (uAUGs) can regulate the translation of downstream ORFs. The AT rich genome of Plasmodium falciparum, due to the higher AT content of start and stop codons, has the potential to give rise to a large number of uORFs and uAUGs that may affect expression of their flanking ORFs.

methodsA bioinformatics approach was used to detect uATGs associated with different genes in the parasite. To study the effect of some of these uAUGs on the expression of the downstream ORF, promoters and 5' leaders containing uAUGs and uORFs were cloned upstream of a luciferase reporter gene. Luciferase assays were carried out in transient transfection experiments to assess the effects of uAUGs and mutations on reporter expression.

resultsThe average number of uATGs and uORFs seen in P. falciparum coding sequences (CDS) is expectedly high compared to other less biased genomes. Certain genes, including the var gene family contain the maximum number of uATGs and uORFs in the parasite. They possess ~5 times more uORFs and ~4.5 times more uAUGs within 100 bases upstream of the start codons than other CDS of the parasite. A 60 bp upstream region containing three ORFs and five ATGs from var gene PF3D7_0400100 and a gene of unknown function (PF3D7_0517100) when cloned upstream of the luciferase start codon, driven by the hsp86 promoter, resulted in loss of luciferase activity. This was restored when all the ATGs present in the -60 bp were mutated to TTGs. Point mutations in the ATGs showed that even one AUG was sufficient to repress the luciferase gene.

conclusionsOverall, this work indicates that the P. falciparum genome has a large number of uATGs and uORFs that can repress the expression of flanking ORFs. The role of AUGs in translation initiation suggests that this repression is mediated by preventing the translation initiation complex from reaching the main AUG of the downstream ORF. How the P. falciparum ribosome is able to bypass these uAUGs and uORFs for highly expressed genes remains a question for future research.

Indexed as

Codon, InitiatorGene Expression RegulationOpen Reading FramesProtein BiosynthesisGene Expression ProfilingGenes, ReporterLuciferasesPlasmodium falciparumCodon, InitiatorLuciferases

Identifiers

PMID26692187
PMCPMC4687322
OpenAlexW2260160227

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.