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 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 UV-Induced Mutation in Neurospora That Affects Translational Regulation in Response to Arginine

Genetics ◽  
1996 ◽  
Vol 142 (1) ◽  
pp. 117-127 ◽  
Author(s):  
Michael Freitag ◽  
Nelima Dighde ◽  
Matthew S Sachs
Keyword(s):  
Translational Control ◽  
Translational Regulation ◽  
Fusion Gene ◽  
Mrna Translation ◽  
Small Subunit ◽  
Upstream Open Reading Frame ◽  
Control Mechanisms ◽  
Carbamoyl Phosphate ◽  
Altered Expression ◽  
Reading Frame

The Neurospora crmsu arg-2 gene encodes the small subunit of arginine-specific carbamoyl phosphate synthetase. The levels of arg-2 mRNA and mRNA translation are negatively regulated by arginine. An upstream open reading frame (uORF) in the transcript’s 5′ region has been implicated in arginine-specific control. An arg-2-hph fusion gene encoding hygromycin phosphotransferase conferred arginine-regulated resistance to hygromycin when introduced into N. crassa. We used an arg-2-hph strain to select for UV-induced mutants that grew in the presence of hygromycin and arginine, and we isolated 46 mutants that had either of two phenotypes. One phenotype indicated altered expression of both arg-2-hph and urg-2 genes; the other, altered expression of urg-2-hph but not arg-2. One of the latter mutations, which was genetically closely linked to arg-2-hph, was recovered from the 5′ region of the arg-2-hph gene using PCR. Sequence analyses and transformation experiments revealed a mutation at uORF codon 12 (Asp to Asn) that abrogated negative regulation. Examination of the distribution of ribosomes on arg-2-hph transcripts showed that loss of regulation had a translational component, indicating the uORF sequence was important for Arg-specific translational control. Comparisons with other uORFS suggest common elements in translational control mechanisms.

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.

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.

A conserved 90 nucleotide element mediates translational repression of nanos RNA

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2791-2800 ◽  
Author(s):  
E.R. Gavis ◽  
L. Lunsford ◽  
S.E. Bergsten ◽  
R. Lehmann
Keyword(s):  
Translational Control ◽  
Untranslated Region ◽  
Translational Regulation ◽  
Critical Role ◽  
Rna Localization ◽  
Translational Repression ◽  
Regulatory Function ◽  
Control Element ◽  
Cis Acting ◽  
Localization Signal

Correct formation of the Drosophila body plan requires restriction of nanos activity to the posterior of the embryo. Spatial regulation of nanos is achieved by a combination of RNA localization and localization-dependent translation such that only posteriorly localized nanos RNA is translated. Cis-acting sequences that mediate both RNA localization and translational regulation lie within the nanos 3′ untranslated region. We have identified a discrete translational control element within the nanos 3′ untranslated region that acts independently of the localization signal to mediate translational repression of unlocalized nanos RNA. Both the translational regulatory function of the nanos 3′UTR and the sequence of the translational control element are conserved between D. melanogaster and D. virilis. Furthermore, we show that the RNA helicase Vasa, which is required for nanos RNA localization, also plays a critical role in promoting nanos translation. Our results specifically exclude models for translational regulation of nanos that rely on changes in polyadenylation.

scholarly journals Translational Control of Protein Kinase Cη by Two Upstream Open Reading Frames

2009 ◽  
Vol 29 (22) ◽  
pp. 6140-6148 ◽  
Author(s):  
Hadas Raveh-Amit ◽  
Adva Maissel ◽  
Jonathan Poller ◽  
Liraz Marom ◽  
Orna Elroy-Stein ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Translational Control ◽  
Translational Regulation ◽  
Normal Growth ◽  
Amino Acid Starvation ◽  
Open Reading Frames ◽  
Pkc Isoforms ◽  
Upstream Open Reading Frames ◽  
Reading Frames

ABSTRACT Protein kinase C (PKC) represents a family of serine/threonine kinases that play a central role in the regulation of cell growth, differentiation, and transformation. Posttranslational control of the PKC isoforms and their activation have been extensively studied; however, not much is known about their translational regulation. Here we report that the expression of one of the PKC isoforms, PKCη, is regulated at the translational level both under normal growth conditions and during stress imposed by amino acid starvation, the latter causing a marked increase in its protein levels. The 5′ untranslated region (5′ UTR) of PKCη is unusually long and GC rich, characteristic of many oncogenes and growth regulatory genes. We have identified two conserved upstream open reading frames (uORFs) in its 5′ UTR and show their effect in suppressing the expression of PKCη in MCF-7 growing cells. While the two uORFs function as repressive elements that maintain low basal levels of PKCη in growing cells, they are required for its enhanced expression upon amino acid starvation. We show that the translational regulation during stress involves leaky scanning and is dependent on eIF-2α phosphorylation by GCN2. Our work further suggests that translational regulation could provide an additional level for controlling the expression of PKC family members, being more common than currently recognized.

Translational termination–re-initiation in viral systems

2008 ◽  
Vol 36 (4) ◽  
pp. 717-722 ◽  
Author(s):  
Michael L. Powell ◽  
T. David K. Brown ◽  
Ian Brierley
Keyword(s):  
Translational Control ◽  
Stop Codon ◽  
Short Review ◽  
Start Codon ◽  
Influenza B ◽  
Control Mechanisms ◽  
Viral Mrnas ◽  
Reading Frame ◽  
Translational Termination ◽  
Stop Codon Readthrough

Viruses have evolved a number of translational control mechanisms to regulate the levels of expression of viral proteins on polycistronic mRNAs, including programmed ribosomal frameshifting and stop codon readthrough. More recently, another unusual mechanism has been described, that of termination-dependent re-initiation (also known as stop–start). Here, the AUG start codon of a 3′ ORF (open reading frame) is proximal to the termination codon of a uORF (upstream ORF), and expression of the two ORFs is coupled. For example, segment 7 mRNA of influenza B is bicistronic, and the stop codon of the M1 ORF and the start codon of the BM2 ORF overlap in the pentanucleotide UAAUG (stop codon of M1 is shown in boldface and start codon of BM2 is underlined). This short review aims to provide some insights into how this translational coupling process is regulated within different viral systems and to highlight some of the differences in the mechanism of re-initiation on prokaryotic, eukaryotic and viral mRNAs.

scholarly journals Control of eukaryotic protein synthesis by upstream open reading frames in the 5′-untranslated region of an mRNA

2002 ◽  
Vol 367 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Hedda A. MEIJER ◽  
Adri A.M. THOMAS
Keyword(s):  
Translational Control ◽  
Untranslated Region ◽  
Developmental Stages ◽  
Mrna Translation ◽  
Open Reading Frames ◽  
Open Reading Frame ◽  
Internal Ribosome Entry ◽  
Control Of Gene Expression ◽  
Reading Frame ◽  
Upstream Open Reading Frames

Control of gene expression is achieved at various levels. Translational control becomes crucial in the absence of transcription, such as occurs in early developmental stages. One of the initiating events in translation is that the 40S subunit of the ribosome binds the mRNA at the 5′-cap structure and scans the 5′-untranslated region (5′-UTR) for AUG initiation codons. AUG codons upstream of the main open reading frame can induce formation of a translation-competent ribosome that may translate and (i) terminate and re-initiate, (ii) terminate and leave the mRNA, resulting in down-regulation of translation of the main open reading frame, or (iii) synthesize an N-terminally extended protein. In the present review we discuss how upstream AUGs can control the expression of the main open reading frame, and a comparison is made with other elements in the 5′-UTR that control mRNA translation, such as hairpins and internal ribosome entry sites. Recent data indicate the flexibility of controlling translation initiation, and how the mode of ribosome entry on the mRNA as well as the elements in the 5′-UTR can accurately regulate the amount of protein synthesized from a specific mRNA.

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.

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