scholarly journals Tuning gene expression with synthetic upstream open reading frames

2013 ◽  
Vol 110 (28) ◽  
pp. 11284-11289 ◽  
Author(s):  
J. P. Ferreira ◽  
K. W. Overton ◽  
C. L. Wang
Keyword(s):  
Gene Expression ◽  
Open Reading Frames ◽  
Upstream Open Reading Frames ◽  
Reading Frames

scholarly journals A First Step towards Learning which uORFs Regulate Gene Expression

2006 ◽  
Vol 3 (2) ◽  
pp. 109-122 ◽  
Author(s):  
◽  
Christopher H. Bryant ◽  
Graham J.L. Kemp ◽  
Marija Cvijovic
Keyword(s):  
Gene Expression ◽  
Inductive Logic ◽  
Preliminary Evidence ◽  
Open Reading Frames ◽  
Yeast Saccharomyces Cerevisiae ◽  
Regulate Gene Expression ◽  
Integrative System ◽  
Upstream Open Reading Frames ◽  
Reading Frames ◽  
Regulate Gene

Summary We have taken a first step towards learning which upstream Open Reading Frames (uORFs) regulate gene expression (i.e., which uORFs are functional) in the yeast Saccharomyces cerevisiae. We do this by integrating data from several resources and combining a bioinformatics tool, ORF Finder, with a machine learning technique, inductive logic programming (ILP). Here, we report the challenge of using ILP as part of this integrative system, in order to automatically generate a model that identifies functional uORFs. Our method makes searching for novel functional uORFs more efficient than random sampling. An attempt has been made to predict novel functional uORFs using our method. Some preliminary evidence that our model may be biologically meaningful is presented.

scholarly journals Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Ivaylo P. Ivanov ◽  
Jiajie Wei ◽  
Stephen Z. Caster ◽  
Kristina M. Smith ◽  
Audrey M. Michel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Neurospora Crassa ◽  
Open Reading Frames ◽  
Reading Frame ◽  
Coding Sequence ◽  
Cell Extracts ◽  
Upstream Open Reading Frames ◽  
Reading Frames

ABSTRACT Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5′ leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5′ region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5′ conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs) in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro . In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression. IMPORTANCE There is a deepening and widening appreciation of the diverse roles of translation in controlling gene expression. A central fungal transcription factor, the best-studied example of which is Saccharomyces cerevisiae GCN4, is crucial for the response to amino acid limitation. Two upstream open reading frames (uORFs) in the GCN4 mRNA are critical for controlling GCN4 synthesis. We observed that two uORFs in the corresponding Neurospora crassa cpc-1 mRNA appear functionally analogous to the GCN4 uORFs. We also discovered that, surprisingly, unlike GCN4, the CPC1 coding sequence extends far upstream from the presumed AUG start codon with no other in-frame AUG codons. Similar extensions were seen in homologs from many filamentous fungi. We observed that multiple non-AUG near-cognate codons (NCCs) in this extended reading frame, some conserved, initiated translation to produce longer forms of CPC1, underscoring the significance of noncanonical initiation in controlling gene expression.

scholarly journals Upstream Open Reading Frames (uORFs) in the Apicomplexan Parasites Plasmodium falciparum and Toxoplasma gondii: Small yet Powerful Regulators of Translation

2021 ◽  
Author(s):  
Chhaminder Kaur ◽  
Swati Patankar
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Toxoplasma Gondii ◽  
Translational Regulation ◽  
Life Cycles ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Apicomplexan Parasites ◽  
Upstream Open Reading Frames ◽  
Reading Frames

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

Analysis of human upstream open reading frames and impact on gene expression

2015 ◽  
Vol 134 (6) ◽  
pp. 605-612 ◽  
Author(s):  
Yuhua Ye ◽  
Yidan Liang ◽  
Qiuxia Yu ◽  
Lingling Hu ◽  
Haoli Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Open Reading Frames ◽  
Upstream Open Reading Frames ◽  
Reading Frames

scholarly journals uORF Shuffling Fine-Tunes Gene Expression at a Deep Level of the Process

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 608
Author(s):  
Yukio Kurihara
Keyword(s):  
Gene Expression ◽  
Deep Level ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Protein Coding ◽  
Polycistronic Mrna ◽  
Upstream Open Reading Frames ◽  
Fine Tune ◽  
Insight Into ◽  
Reading Frames

Upstream open reading frames (uORFs) are present in the 5’ leader sequences (or 5’ untranslated regions) upstream of the protein-coding main ORFs (mORFs) in eukaryotic polycistronic mRNA. It is well known that a uORF negatively affects translation of the mORF. Emerging ribosome profiling approaches have revealed that uORFs themselves, as well as downstream mORFs, can be translated. However, it has also been revealed that plants can fine-tune gene expression by modulating uORF-mediated regulation in some situations. This article reviews several proposed mechanisms that enable genes to escape from uORF-mediated negative regulation and gives insight into the application of uORF-mediated regulation for precisely controlling gene expression.

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