scholarly journals uORFs: Important Cis-Regulatory Elements in Plants

2020 ◽  
Vol 21 (17) ◽  
pp. 6238
Author(s):  
Ting Zhang ◽  
Anqi Wu ◽  
Yaping Yue ◽  
Yu Zhao
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Translational Regulation ◽  
Regulatory Elements ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Post Translational Modification ◽  
Cis Acting ◽  
Eukaryotic Mrnas

Gene expression is regulated at many levels, including mRNA transcription, translation, and post-translational modification. Compared with transcriptional regulation, mRNA translational control is a more critical step in gene expression and allows for more rapid changes of encoded protein concentrations in cells. Translation is highly regulated by complex interactions between cis-acting elements and trans-acting factors. Initiation is not only the first phase of translation, but also the core of translational regulation, because it limits the rate of protein synthesis. As potent cis-regulatory elements in eukaryotic mRNAs, upstream open reading frames (uORFs) generally inhibit the translation initiation of downstream major ORFs (mORFs) through ribosome stalling. During the past few years, with the development of RNA-seq and ribosome profiling, functional uORFs have been identified and characterized in many organisms. Here, we review uORF identification, uORF classification, and uORF-mediated translation initiation. More importantly, we summarize the translational regulation of uORFs in plant metabolic pathways, morphogenesis, disease resistance, and nutrient absorption, which open up an avenue for precisely modulating the plant growth and development, as well as environmental adaption. Additionally, we also discuss prospective applications of uORFs in plant breeding.

scholarly journals Translational control of fungal gene expression during the wheat-Fusarium graminearum interaction

2021 ◽  
Author(s):  
UDAYKUMAR KAGE ◽  
Donald Gardiner ◽  
Jiri S Stiller ◽  
Kemal Kazan
Keyword(s):  
Gene Expression ◽  
Fusarium Graminearum ◽  
Translational Control ◽  
Fungal Pathogen ◽  
Translational Regulation ◽  
Fungal Pathogens ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Head Blight ◽  
Fungal Virulence

To date, translational regulation of key genes controlling infection-related processes in fungal pathogens during their interactions with plants has not been studied. Here, we employed ribosome profiling (ribo-seq) to study translational responses and how such responses are coordinated with transcriptional changes in the fungal pathogen Fusarium graminearum (Fg), which causes Fusarium head blight (FHB), a destructive disease of cereal crops worldwide. Transcription and translation were not always coordinated with approximately 22% of Fg genes showing a discordant relationship during wheat infection. Nitrite reductase, which we show here as an important component of fungal virulence, is only regulated at the translational level in Fg. In addition, more than 1000 new open reading frames (ORFs), many of which are short and highly conserved, were identified in the Fg genome. Like in higher eukaryotes, translation is controlled by upstream ORFs (uORFs) in Fg during infection. Similarly, miRNAs control both transcription and translation in Fg during wheat infection. However, Fgdicer2-dependent miRNAs do not have a significant effect on transcriptional gene expression at the global outset. The ribo-seq study undertaken here for the first time in any fungal pathogen discovered novel insights about the biology of an important plant pathogen.

scholarly journals Translation of ABCE1 Is Tightly Regulated by Upstream Open Reading Frames in Human Colorectal Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 911
Author(s):  
Joana Silva ◽  
Pedro Nina ◽  
Luísa Romão
Keyword(s):  
Translational Regulation ◽  
Regulatory Elements ◽  
Ribosome Profiling ◽  
Leader Sequence ◽  
Open Reading Frames ◽  
Regulatory Function ◽  
Coding Sequence ◽  
Abc Protein ◽  
Upstream Open Reading Frames ◽  
Reading Frames

ATP-binding cassette subfamily E member 1 (ABCE1) belongs to the ABC protein family of transporters; however, it does not behave as a drug transporter. Instead, ABCE1 actively participates in different stages of translation and is also associated with oncogenic functions. Ribosome profiling analysis in colorectal cancer cells has revealed a high ribosome occupancy in the human ABCE1 mRNA 5′-leader sequence, indicating the presence of translatable upstream open reading frames (uORFs). These cis-acting translational regulatory elements usually act as repressors of translation of the main coding sequence. In the present study, we dissect the regulatory function of the five AUG and five non-AUG uORFs identified in the human ABCE1 mRNA 5′-leader sequence. We show that the expression of the main coding sequence is tightly regulated by the ABCE1 AUG uORFs in colorectal cells. Our results are consistent with a model wherein uORF1 is efficiently translated, behaving as a barrier to downstream uORF translation. The few ribosomes that can bypass uORF1 (and/or uORF2) must probably initiate at the inhibitory uORF3 or uORF5 that efficiently repress translation of the main ORF. This inhibitory property is slightly overcome in conditions of endoplasmic reticulum stress. In addition, we observed that these potent translation-inhibitory AUG uORFs function equally in cancer and in non-tumorigenic colorectal cells, which is consistent with a lack of oncogenic function. In conclusion, we establish human ABCE1 as an additional example of uORF-mediated translational regulation and that this tight regulation contributes to control ABCE1 protein levels in different cell environments.

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.

scholarly journals uORFlight: a vehicle toward uORF-mediated translational regulation mechanisms in eukaryotes

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Ruixia Niu ◽  
Yulu Zhou ◽  
Yu Zhang ◽  
Rui Mou ◽  
Zhijuan Tang ◽  
...  
Keyword(s):  
Translational Control ◽  
Translational Regulation ◽  
Homo Sapiens ◽  
Phenotypic Diversity ◽  
Relevant Literature ◽  
Open Reading Frames ◽  
Control Element ◽  
Control Mechanisms ◽  
Reading Frame ◽  
Eukaryotic Mrnas

Abstract Upstream open reading frames (uORFs) are prevalent in eukaryotic mRNAs. They act as a translational control element for precisely tuning the expression of the downstream major open reading frame (mORF). uORF variation has been clearly associated with several human diseases. In contrast, natural uORF variants in plants have not ever been identified or linked with any phenotypic changes. The paucity of such evidence encouraged us to generate this database-uORFlight (http://uorflight.whu.edu.cn). It facilitates the exploration of uORF variation among different splicing models of Arabidopsis and rice genes. Most importantly, users can evaluate uORF frequency among different accessions at the population scale and find out the causal single nucleotide polymorphism (SNP) or insertion/deletion (INDEL), which can be associated with phenotypic variation through database mining or simple experiments. Such information will help to make hypothesis of uORF function in plant development or adaption to changing environments on the basis of the cognate mORF function. This database also curates plant uORF relevant literature into distinct groups. To be broadly interesting, our database expands uORF annotation into more species of fungus (Botrytis cinerea and Saccharomyces cerevisiae), plant (Brassica napus, Glycine max, Gossypium raimondii, Medicago truncatula, Solanum lycopersicum, Solanum tuberosum, Triticum aestivum and Zea mays), metazoan (Caenorhabditis elegans and Drosophila melanogaster) and vertebrate (Homo sapiens, Mus musculus and Danio rerio). Therefore, uORFlight will light up the runway toward how uORF genetic variation determines phenotypic diversity and advance our understanding of translational control mechanisms in eukaryotes.

scholarly journals A spatiotemporal translatome of mouse tissue development

2020 ◽  
Author(s):  
Hongwei Wang ◽  
Yan Wang ◽  
Jiaqi Yang ◽  
Nan Tang ◽  
Huihui Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Translational Control ◽  
Translational Regulation ◽  
Regulation Of Gene Expression ◽  
Open Reading Frames ◽  
Mouse Tissue ◽  
Specific Gene ◽  
Translational Efficiency ◽  
Tissue Development ◽  
Mouse Tissues

AbstractThe precise regulation of gene expression in mammalian tissues during development results in their functional specification. Although previous transcriptomic and proteomic analyses have provided great biological insights into tissue-specific gene expression and the physiological relevance of these tissues in development, our understanding of translational regulation in developing tissues is lacking. In this study, we performed a spatiotemporally resolved translatome analysis of six mouse tissues at the embryonic and adult stages to quantify the effects of translational regulation and identify new translational components. We quantified the spatial and temporal divergences of gene expression and detected specific changes in gene expression and pathways underlying these divergences. We further showed that dynamic translational control can be achieved by modulating the translational efficiency, which resulted in the enhancement of tissue specificity during development. We also discovered thousands of actively translated upstream open reading frames (ORFs) that exhibited spatiotemporal patterns and demonstrated their regulatory roles in translational regulation. Furthermore, we identified known and novel micropeptides encoded by small ORFs from long noncoding RNAs that are functionally relevant to tissue development. Our data and analyses facilitate a better understanding of the complexity of translational regulation across tissue and developmental spectra and serve as a useful resource of the mouse translatome.

scholarly journals uORFlight: a vehicle towards uORF-mediated translational regulation mechanisms in eukaryotes

2019 ◽  
Author(s):  
Ruixia Niu ◽  
Yulu Zhou ◽  
Rui Mou ◽  
Zhijuan Tang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Translational Control ◽  
Translational Regulation ◽  
Homo Sapiens ◽  
Phenotypic Diversity ◽  
Relevant Literature ◽  
Open Reading Frames ◽  
Control Element ◽  
Control Mechanisms ◽  
Reading Frame ◽  
Eukaryotic Mrnas

AbstractUpstream open reading frames (uORFs) are prevalent in eukaryotic mRNAs. They act as a translational control element for precisely tuning the expression of the downstream major open reading frame (mORF) with essential cellular functionalities. uORF variation has been clearly associated with several human diseases. In contrast, natural uORF variants in plants have not ever been identified or linked with any phenotypic changes. The paucity of such evidence encouraged us to generate this database-uORFlight (http://uorflight.whu.edu.cn). It facilitates the exploration of uORF variation among different splicing models of Arabidopsis and rice genes. Most importantly, users can evaluate uORF frequency among different accessions at the population scale and find out the causal single nucleotide polymorphism (SNP) or insertion/deletion (INDEL) which can be associated with phenotypic variation through database mining or simple experiments. Such information will help to make hypotheses of uORF function in plant development or adaption to changing environments on the basis of the cognate mORF function. This database also curates plant uORF relevant literature into distinct groups. To be broadly interesting, our database expands uORF annotation into more species of fungi (Botrytis cinerea), plant (Brassica napus, Glycine max, Gossypium raimondii, Medicago truncatula, Solanum lycopersicum, Solanum tuberosum, Triticum aestivum and Zea mays), metazoan (Caenorhabditis elegans and Drosophila melanogaster) and vertebrate (Homo sapiens, Mus musculus and Danio rerio). Therefore, uORFlight will light up the runway toward how uORF genetic variation determines phenotypic diversity and advance our understanding of translational control mechanisms.

scholarly journals CFTR Cooperative Cis-Regulatory Elements in Intestinal Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2599
Author(s):  
Mégane Collobert ◽  
Ozvan Bocher ◽  
Anaïs Le Nabec ◽  
Emmanuelle Génin ◽  
Claude Férec ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Gene Regulation ◽  
Genetic Diseases ◽  
Regulatory Elements ◽  
Cftr Gene ◽  
Intestinal Cells ◽  
Cooperative Effects ◽  
Cis Acting ◽  
Study Techniques

About 8% of the human genome is covered with candidate cis-regulatory elements (cCREs). Disruptions of CREs, described as “cis-ruptions” have been identified as being involved in various genetic diseases. Thanks to the development of chromatin conformation study techniques, several long-range cystic fibrosis transmembrane conductance regulator (CFTR) regulatory elements were identified, but the regulatory mechanisms of the CFTR gene have yet to be fully elucidated. The aim of this work is to improve our knowledge of the CFTR gene regulation, and to identity factors that could impact the CFTR gene expression, and potentially account for the variability of the clinical presentation of cystic fibrosis as well as CFTR-related disorders. Here, we apply the robust GWAS3D score to determine which of the CFTR introns could be involved in gene regulation. This approach highlights four particular CFTR introns of interest. Using reporter gene constructs in intestinal cells, we show that two new introns display strong cooperative effects in intestinal cells. Chromatin immunoprecipitation analyses further demonstrate fixation of transcription factors network. These results provide new insights into our understanding of the CFTR gene regulation and allow us to suggest a 3D CFTR locus structure in intestinal cells. A better understand of regulation mechanisms of the CFTR gene could elucidate cases of patients where the phenotype is not yet explained by the genotype. This would thus help in better diagnosis and therefore better management. These cis-acting regions may be a therapeutic challenge that could lead to the development of specific molecules capable of modulating gene expression in the future.

scholarly journals The Role of Translation Initiation Regulation in Haematopoiesis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Control ◽  
Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences

1988 ◽  
Vol 8 (9) ◽  
pp. 3827-3836
Author(s):  
N P Williams ◽  
P P Mueller ◽  
A G Hinnebusch
Keyword(s):  
Translational Control ◽  
Normal Growth ◽  
Regulatory Elements ◽  
Growth Conditions ◽  
Open Reading Frames ◽  
Regulatory Function ◽  
Yeast Saccharomyces Cerevisiae ◽  
Reading Frame ◽  
Yeast Genes ◽  
Reading Frames

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function.

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