scholarly journals Negative and Translation Termination-Dependent Positive Control of FLI-1 Protein Synthesis by Conserved Overlapping 5′ Upstream Open Reading Frames in Fli-1 mRNA

2000 ◽  
Vol 20 (9) ◽  
pp. 2959-2969 ◽  
Author(s):  
Sandrine Sarrazin ◽  
Joëlle Starck ◽  
Colette Gonnet ◽  
Alexandre Doubeikovski ◽  
Fabrice Melet ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Translation Termination ◽  
Mrna Translation ◽  
Positive Control ◽  
Open Reading Frames ◽  
Protein Isoforms ◽  
Erythroid Cell ◽  
Upstream Open Reading Frames ◽  
Reading Frames

ABSTRACT The proto-oncogene Fli-1 encodes a transcription factor of the ets family whose overexpression is associated with multiple virally induced leukemias in mouse, inhibits murine and avian erythroid cell differentiation, and induces drastic perturbations of early development in Xenopus. This study demonstrates the surprisingly sophisticated regulation of Fli-1 mRNA translation. We establish that two FLI-1 protein isoforms (of 51 and 48 kDa) detected by Western blotting in vivo are synthesized by alternative translation initiation through the use of two highly conserved in-frame initiation codons, AUG +1 and AUG +100. Furthermore, we show that the synthesis of these two FLI-1 isoforms is regulated by two short overlapping 5′ upstream open reading frames (uORF) beginning at two highly conserved upstream initiation codons, AUG −41 and GUG −37, and terminating at two highly conserved stop codons, UGA +35 and UAA +15. The mutational analysis of these two 5′ uORF revealed that each of them negatively regulates FLI-1 protein synthesis by precluding cap-dependent scanning to the 48- and 51-kDa AUG codons. Simultaneously, the translation termination of the two 5′ uORF appears to enhance 48-kDa protein synthesis, by allowing downstream reinitiation at the 48-kDa AUG codon, and 51-kDa protein synthesis, by allowing scanning ribosomes to pile up and consequently allowing upstream initiation at the 51-kDa AUG codon. To our knowledge, this is the first example of a cellular mRNA displaying overlapping 5′ uORF whose translation termination appears to be involved in the positive control of translation initiation at both downstream and upstream initiation codons.

Translational regulation of the plant S-adenosylmethionine decarboxylase

2003 ◽  
Vol 31 (2) ◽  
pp. 424-427 ◽  
Author(s):  
C. Hanfrey ◽  
M. Franceschetti ◽  
M.J. Mayer ◽  
C. Illingworth ◽  
K. Elliott ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Rna Secondary Structure ◽  
Translational Regulation ◽  
Mrna Translation ◽  
Open Reading Frames ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Key Enzyme ◽  
Upstream Open Reading Frames ◽  
Reading Frames

It is becoming apparent that control of protein synthesis by metabolites is more common than previously thought. Much of that control is exerted at the level of initiation of mRNA translation, orchestrated by upstream open reading frames (uORFs) and RNA secondary structure. S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in polyamine biosynthesis and both mammalian and plant AdoMetDCs are translationally regulated by uORFs in response to polyamine levels by distinct mechanisms.

scholarly journals Control of MYEOV Protein Synthesis by Upstream Open Reading Frames

2005 ◽  
Vol 281 (2) ◽  
pp. 695-704 ◽  
Author(s):  
Rogério Alves de Almeida ◽  
Tanja Heuser ◽  
Rüdiger Blaschke ◽  
Claus R. Bartram ◽  
Johannes W. G. Janssen
Keyword(s):  
Protein Synthesis ◽  
Open Reading Frames ◽  
Upstream Open Reading Frames ◽  
Reading Frames

scholarly journals Near-Cognate Codons Contribute Complexity to Translation Regulation

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
N. Louise Glass
Keyword(s):  
Protein Synthesis ◽  
Cell Fate ◽  
Translation Initiation ◽  
Cellular Response ◽  
Open Reading Frames ◽  
Translation Regulation ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Upstream Open Reading Frames ◽  
Response To Stress

ABSTRACT The interplay between translation initiation, modification of translation initiation factors, and selection of start sites on mRNA for protein synthesis can play a regulatory role in the cellular response to stress, development, and cell fate in eukaryotic species by shaping the proteome. As shown by Ivanov et al. (mBio 8:e00844-17, 2017, https://doi.org/10.1128/mBio.00844-17 !), in the filamentous fungus Neurospora crassa, both upstream open reading frames (uORFs) and near-cognate start codons negatively or positively regulate the translation of the transcription factor CPC1 and production of CPC1 isoforms, which mediate the cellular response to amino acid starvation. Dissecting the physiological roles that differentiate cellular choice of translation initiation is an important parameter to understanding mechanisms that determine cell fate via gene regulation and protein synthesis.

scholarly journals Extending the spacing between the Shine-Dalgarno sequence and P-site codon reduces the rate of mRNA translocation

2020 ◽  
Author(s):  
Hironao Wakabayashi ◽  
Chandani Warnasooriya ◽  
Dmitri N. Ermolenko
Keyword(s):  
Protein Synthesis ◽  
16S Rrna ◽  
Translation Initiation ◽  
Open Reading Frames ◽  
Structural Rearrangements ◽  
Spacer Length ◽  
Fold Reduction ◽  
Shine Dalgarno Sequence ◽  
Elongation Phase ◽  
Reading Frames

By forming basepairing interactions with the 3’ end of 16S rRNA, mRNA Shine-Dalgarno (SD) sequences positioned upstream of Open Reading Frames (ORFs) facilitate translation initiation. During the elongation phase of protein synthesis, intragenic SD-like sequences stimulate ribosome frameshifting and may also slow down ribosome movement along mRNA. Here, we show that the length of the spacer between the SD sequence and P-site codon strongly affects the rate of ribosome translocation. Increasing the spacer length beyond six nucleotides destabilizes mRNA-ribosome interactions and results in a 5-10 fold reduction of the translocation rate. These observations suggest that during translation, the spacer between the SD sequence and P-site codon undergoes structural rearrangements, which slow down mRNA translocation and promote mRNA frameshifting.

scholarly journals Plants Utilise Ancient Conserved Peptide Upstream Open Reading Frames as Environmental Sensors

2021 ◽  
Author(s):  
Barry Causier ◽  
Tayah Hopes ◽  
Mary McKay ◽  
Zachary Paling ◽  
Brendan Davies
Keyword(s):  
Protein Synthesis ◽  
Growth And Development ◽  
Open Reading Frames ◽  
Environmental Sensors ◽  
Environmental Signals ◽  
Broad Application ◽  
Ribosome Stalling ◽  
Mrna Transcripts ◽  
Upstream Open Reading Frames ◽  
Reading Frames

The regulation of protein synthesis plays an important role in growth and development in all organisms. Upstream open reading frames (uORFs) are commonly found in eukaryotic mRNA transcripts and typically attenuate the translation of associated downstream main ORFs (mORFs). Conserved peptide uORFs (CPuORFs) are a rare subset of uORFs, some of which have been shown to conditionally regulate translation by ribosome stalling. Here we identify three Arabidopsis CPuORFs of ancient origin that regulate translation of any downstream ORF, in response to agriculturally significant environmental signals: heat stress and water limitation. We provide evidence that different sequence classes of CPuORF stall ribosomes during different phases of translation and show that plant CPuORFs act as environmental sensors that can be utilised as inducible regulators of translation with broad application.

scholarly journals Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer’s disease

2021 ◽  
Vol 14 (668) ◽  
pp. eabc5429
Author(s):  
Mauricio M. Oliveira ◽  
Mychael V. Lourenco ◽  
Francesco Longo ◽  
Nicole P. Kasica ◽  
Wenzhong Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Postmortem Brain Tissue ◽  
Phosphorylated Eif2α

Neuronal protein synthesis is essential for long-term memory consolidation, and its dysregulation is implicated in various neurodegenerative disorders, including Alzheimer’s disease (AD). Cellular stress triggers the activation of protein kinases that converge on the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), which attenuates mRNA translation. This translational inhibition is one aspect of the integrated stress response (ISR). We found that postmortem brain tissue from AD patients showed increased phosphorylation of eIF2α and reduced abundance of eIF2B, another key component of the translation initiation complex. Systemic administration of the small-molecule compound ISRIB (which blocks the ISR downstream of phosphorylated eIF2α) rescued protein synthesis in the hippocampus, measures of synaptic plasticity, and performance on memory-associated behavior tests in wild-type mice cotreated with salubrinal (which inhibits translation by inducing eIF2α phosphorylation) and in both β-amyloid-treated and transgenic AD model mice. Thus, attenuating the ISR downstream of phosphorylated eIF2α may restore hippocampal protein synthesis and delay cognitive decline in AD patients.

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.

Sign in / Sign up

Export Citation Format

Share Document