scholarly journals Differential Neuroendocrine Expression of Multiple Brain-Derived Neurotrophic Factor Transcripts

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1361-1368 ◽  
Author(s):  
Adhanet H. Kidane ◽  
Gerhard Heinrich ◽  
Ron P. H. Dirks ◽  
Brechje A. de Ruyck ◽  
Nicolette H. Lubsen ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Open Reading Frames ◽  
White Background ◽  
Translation Efficiency ◽  
Bdnf Gene ◽  
Black Background ◽  
Upstream Open Reading Frames ◽  
Reading Frames

Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important growth-promoting properties. We report here the first characterization of a BDNF gene in an amphibian, Xenopus laevis, and demonstrate that environmental factors can activate this gene in a promoter-specific fashion. The Xenopus BDNF gene contains six promoter-specific 5′-exons and one 3′-protein-encoding exon. We examined the expression of promoter-specific transcripts in Xenopus neuroendocrine melanotrope cells. These cells make a good model to study how environmental factors control gene expression. In animals placed on a black background melanotrope cells more actively produce and release αMSH than in animals on a white background. BDNF is cosequestered and coreleased with αMSH and stimulates biosynthesis of proopiomelanocortin (POMC), the precursor protein for αMSH. Our analysis of the expression of the BDNF transcripts revealed that there is differential use of some BDNF promoters in melanotrope cells, depending on the adaptation state of the frog. During black-background adaptation, stimulation of expression of BDNF transcript IV preceded that of the POMC transcript, suggesting the BDNF gene is an effector gene for POMC expression. The possible mechanisms regulating expression of the various transcripts are discussed on the basis of the potential calcium- and cAMP-responsive elements in the promoter region of exon IV. Finally, we show that the upstream open reading frames of BDNF transcripts I and IV markedly decrease BDNF translation efficiency, giving the first indication for a functional role of untranslated BDNF exons. We show promoter-specific expression of BDNF transcripts in neuroendocrine melanotrope cells and provide evidence that upstream open reading frames of BDNF transcripts decrease translation efficiency.

scholarly journals DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan Bohlen ◽  
Liza Harbrecht ◽  
Saioa Blanco ◽  
Katharina Clemm von Hohenberg ◽  
Kai Fenzl ◽  
...  
Keyword(s):  
Stress Response ◽  
Cancer Cells ◽  
Strong Correlation ◽  
Molecular Mechanisms ◽  
Open Reading Frames ◽  
Translation Efficiency ◽  
Dependent Manner ◽  
Translation Factors ◽  
Upstream Open Reading Frames ◽  
Reading Frames

Abstract Translation efficiency varies considerably between different mRNAs, thereby impacting protein expression. Translation of the stress response master-regulator ATF4 increases upon stress, but the molecular mechanisms are not well understood. We discover here that translation factors DENR, MCTS1 and eIF2D are required to induce ATF4 translation upon stress by promoting translation reinitiation in the ATF4 5′UTR. We find DENR and MCTS1 are only needed for reinitiation after upstream Open Reading Frames (uORFs) containing certain penultimate codons, perhaps because DENR•MCTS1 are needed to evict only certain tRNAs from post-termination 40S ribosomes. This provides a model for how DENR and MCTS1 promote translation reinitiation. Cancer cells, which are exposed to many stresses, require ATF4 for survival and proliferation. We find a strong correlation between DENR•MCTS1 expression and ATF4 activity across cancers. Furthermore, additional oncogenes including a-Raf, c-Raf and Cdk4 have long uORFs and are translated in a DENR•MCTS1 dependent manner.

Analysis of plant mRNA upstream open reading frames

2005 ◽  
Vol 2 (1) ◽  
pp. 59-66
Author(s):  
Jin Yong-Feng ◽  
Jin Hui-Qing ◽  
Zhou Ping ◽  
Bian Teng-Fei
Keyword(s):  
Plant Species ◽  
Open Reading Frames ◽  
Untranslated Regions ◽  
Translation Efficiency ◽  
Consensus Sequences ◽  
Codon Context ◽  
Eukaryotic Mrnas ◽  
Upstream Open Reading Frames ◽  
Regulatory Functions ◽  
Reading Frames

AbstractUpstream open reading frames (uORFs) in 5′-untranslated regions (5′-UTRs) of eukaryotic mRNAs play an important role in translation efficiency. Computational analysis of the upstream ATG (uATG) and uORFs of 5′-UTRs of plant mRNAs, adopted from the nucleotide sequence databank, was carried out. Statistical analysis revealed that up to 18% of 5′-UTRs contain uATG, which is much higher than the earlier estimate. Among them, about 50% of the genes have one uATG and nearly 20% of them have two uATGs. About 85% of uORFs are non-overlapping. Thirty per cent of uORF peptides comprise 1–5 aa, and about 80% of uORFs fall in the range of below 20 aa. Sequences flanking the uATG codon differ strikingly from the functional initiation codon and the uATG triplet is more frequently located in a non-optimal context. Consensus sequences of the ATG codon context of mRNA with and without uATG are similar, whereas the ATG codon context of mRNA without uATG is more frequently located in an optimal context than is mRNA with uATG. Most mRNAs with uATGs are possibly related to regulatory functions. In addition, most mRNA uORFs have no similarity between plant species whereas sequences of a few uORFs are highly conserved. For example, mRNA uORFs encoding S-adenosyl-l-methionine decarboxylase (AdoMetDC) share 75–100% homology between plant species, which is much more conserved than AdoMetDC protein.

Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames

2016 ◽  
Vol 34 (8) ◽  
pp. 875-880 ◽  
Author(s):  
Xue-hai Liang ◽  
Wen Shen ◽  
Hong Sun ◽  
Michael T Migawa ◽  
Timothy A Vickers ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Open Reading Frames ◽  
Translation Efficiency ◽  
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 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.

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