3´ Untranslated Regions of c-myc and c-fos mRNAs: Multifunctional Elements Regulating mRNA Translation, Degradation and Subcellular Localization

Author(s):  
J. L. Veyrune ◽  
J. Hesketh ◽  
J. M. Blanchard
2020 ◽  
Vol 375 (1795) ◽  
pp. 20190344 ◽  
Author(s):  
Lynne E. Maquat

Primate-specific Alu short interspersed nuclear elements (SINEs) and rodent-specific B and ID (B/ID) SINEs are non-autonomous and generally non-coding retrotransposons that have been copied and pasted into the respective genomes so as to constitute what is estimated to be a remarkable 13% and 8% of those genomes. In the context of messenger RNAs (mRNAs), those residing within 3′-untranslated regions (3′UTRs) can influence mRNA export from the nucleus to the cytoplasm, mRNA translation and/or mRNA decay via proteins with which they associate either individually or base-paired in cis or in trans with a partially complementary SINE. Each of these influences impinges on the primary function of mRNA, which is to serve as a template for protein synthesis. This review describes how human cells have used 3′UTR Alu elements to mediate post-transcriptional gene regulation and also describes examples of convergent evolution between human and mouse 3′UTR SINEs. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.


2006 ◽  
Vol 34 (1) ◽  
pp. 12-16 ◽  
Author(s):  
T.L. Hamilton ◽  
M. Stoneley ◽  
K.A. Spriggs ◽  
M. Bushell

Upon cell-cycle arrest or nutrient deprivation, the cellular rate of ribosome production is reduced significantly. In mammalian cells, this effect is achieved in part through a co-ordinated inhibition of RP (ribosomal protein) synthesis. More specifically, translation initiation on RP mRNAs is inhibited. Translational regulation of RP synthesis is dependent on cis-elements within the 5′-UTRs (5′-untranslated regions) of the RP mRNAs. In particular, a highly conserved 5′-TOP (5′-terminal oligopyrimidine tract) appears to play a key role in the regulation of RP mRNA translation. This article explores recent developments in our understanding of the mechanism of TOP mRNA regulation, focusing on upstream signalling pathways and trans-acting factors, and highlighting some interesting observations which have come to light following the recent development of cDNA microarray technology coupled with polysome analysis.


2021 ◽  
Author(s):  
Hsin-Yen Larry Wu ◽  
Polly Yingshan Hsu

Abstract Background: Ribo-seq has revolutionized the study of genome-wide mRNA translation. High-quality Ribo-seq data display strong 3-nucleotide (nt) periodicity, which corresponds to translating ribosomes deciphering three nts at a time. While 3-nt periodicity has been widely used to study novel translation events such as upstream ORFs in 5’ untranslated regions and small ORFs in presumed non-coding RNAs, tools that allow the visualization of these events remain underdeveloped.Results: RiboPlotR is a visualization package written in R that presents both RNA-seq coverage and Ribo-seq reads in genomic coordinates for all annotated transcript isoforms of a gene. Specifically, for individual isoform models, RiboPlotR plots Ribo-seq data related to splice junctions and presents the reads for all three reading frames in three different colors. Moreover, RiboPlotR shows Ribo-seq reads in upstream ORFs, 5' and 3' untranslated regions and introns, which is critical for observing new translation events and identifying potential regulatory mechanisms.Conclusions: RiboPlotR is freely available (https://github.com/hsinyenwu/RiboPlotR and https://sourceforge.net/projects/riboplotr/) and allows the visualization of translated features identified in Ribo-seq data.


2019 ◽  
Vol 20 (18) ◽  
pp. 4464 ◽  
Author(s):  
Nikolay E. Shirokikh ◽  
Yulia S. Dutikova ◽  
Maria A. Staroverova ◽  
Ross D. Hannan ◽  
Thomas Preiss

Several control mechanisms of eukaryotic gene expression target the initiation step of mRNA translation. The canonical translation initiation pathway begins with cap-dependent attachment of the small ribosomal subunit (SSU) to the messenger ribonucleic acid (mRNA) followed by an energy-dependent, sequential ‘scanning’ of the 5′ untranslated regions (UTRs). Scanning through the 5′UTR requires the adenosine triphosphate (ATP)-dependent RNA helicase eukaryotic initiation factor (eIF) 4A and its efficiency contributes to the specific rate of protein synthesis. Thus, understanding the molecular details of the scanning mechanism remains a priority task for the field. Here, we studied the effects of inhibiting ATP-dependent translation and eIF4A in cell-free translation and reconstituted initiation reactions programmed with capped mRNAs featuring different 5′UTRs. An aptamer that blocks eIF4A in an inactive state away from mRNA inhibited translation of capped mRNA with the moderately structured β-globin sequences in the 5′UTR but not that of an mRNA with a poly(A) sequence as the 5′UTR. By contrast, the nonhydrolysable ATP analogue β,γ-imidoadenosine 5′-triphosphate (AMP-PNP) inhibited translation irrespective of the 5′UTR sequence, suggesting that complexes that contain ATP-binding proteins in their ATP-bound form can obstruct and/or actively block progression of ribosome recruitment and/or scanning on mRNA. Further, using primer extension inhibition to locate SSUs on mRNA (‘toeprinting’), we identify an SSU complex which inhibits primer extension approximately eight nucleotides upstream from the usual toeprinting stop generated by SSUs positioned over the start codon. This ‘−8 nt toeprint’ was seen with mRNA 5′UTRs of different length, sequence and structure potential. Importantly, the ‘−8 nt toeprint’ was strongly stimulated by the presence of the cap on the mRNA, as well as the presence of eIFs 4F, 4A/4B and ATP, implying active scanning. We assembled cell-free translation reactions with capped mRNA featuring an extended 5′UTR and used cycloheximide to arrest elongating ribosomes at the start codon. Impeding scanning through the 5′UTR in this system with elevated magnesium and AMP-PNP (similar to the toeprinting conditions), we visualised assemblies consisting of several SSUs together with one full ribosome by electron microscopy, suggesting direct detection of scanning intermediates. Collectively, our data provide additional biochemical, molecular and physical evidence to underpin the scanning model of translation initiation in eukaryotes.


2019 ◽  
Author(s):  
Hsin-Yen Larry Wu ◽  
Polly Yingshan Hsu

ABSTRACTBackgroundRibo-seq has revolutionized the study of mRNA translation in a genome-wide scale. High-quality Ribo-seq data display strong 3-nucleotide (nt) periodicity, which corresponds to translating ribosomes decipher three nucleotides each time. While the 3-nt periodicity has been widely used to study novel translation events and identify small open reading frames on presumed non-coding RNAs, tools which allow the visualization of those events remain underdeveloped.FindingsRiboPlotR is a visualization package written in R that presents both RNA-seq coverage and Ribo-seq reads for all annotated transcript isoforms in a context of a given gene. In particular, RiboPlotR plots Ribo-seq reads mapped in three reading frames using three colors for one isoform model at a time. Moreover, RiboPlotR shows Ribo-seq reads on upstream ORFs, 5’ and 3’ untranslated regions and introns, which is critical for observing new translation events and potential regulatory mechanisms.ConclusionsRiboPlotR is freely available (https://github.com/hsinyenwu/RiboPlotR) and allows the visualization of the translating features in Ribo-seq data.


PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0145998 ◽  
Author(s):  
Matthieu Gratia ◽  
Patrice Vende ◽  
Annie Charpilienne ◽  
Hilma Carolina Baron ◽  
Cécile Laroche ◽  
...  

Plant Methods ◽  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hsin-Yen Larry Wu ◽  
Polly Yingshan Hsu

Abstract Background Ribo-seq has revolutionized the study of genome-wide mRNA translation. High-quality Ribo-seq data display strong 3-nucleotide (nt) periodicity, which corresponds to translating ribosomes deciphering three nts at a time. While 3-nt periodicity has been widely used to study novel translation events such as upstream ORFs in 5′ untranslated regions and small ORFs in presumed non-coding RNAs, tools that allow the visualization of these events remain underdeveloped. Results RiboPlotR is a visualization package written in R that presents both RNA-seq coverage and Ribo-seq reads in genomic coordinates for all annotated transcript isoforms of a gene. Specifically, for individual isoform models, RiboPlotR plots Ribo-seq data in the context of gene structures, including 5′ and 3′ untranslated regions and introns, and it presents the reads for all three reading frames in three different colors. The inclusion of gene structures and color-coding the reading frames facilitate observing new translation events and identifying potential regulatory mechanisms. Conclusions RiboPlotR is freely available (https://github.com/hsinyenwu/RiboPlotR and https://sourceforge.net/projects/riboplotr/) and allows the visualization of translated features identified in Ribo-seq data.


2009 ◽  
Vol 296 (6) ◽  
pp. E1230-E1238 ◽  
Author(s):  
Mi-Jeong Lee ◽  
Susan K. Fried

This review summarizes recent advances in our understanding of the pre- and posttranscriptional mechanisms that regulate leptin production and secretion in adipocytes. Basal leptin production is proportional to the status of energy stores, i.e., fat cell size, and this is mainly regulated by alterations in leptin mRNA levels. Leptin mRNA levels are regulated by hormones, including glucocorticoids and catecholamines, but little is known about the transcriptional mechanisms involved. Leptin synthesis and secretion is also acutely modulated in response to hormones such as insulin and the availability of metabolic fuels. Acute variations in leptin production over a time course of minutes to hours are mediated at the levels of both translation and secretion. Increases in amino acids and insulin after a meal activate the mammalian target of rapamycin (mTOR) pathway, leading to an increase in specific rates of leptin biosynthesis. Cross-talk among mTOR, PKA, and AMP-activated protein kinase pathways appears to integrate hormonal and nutrient signals that regulate leptin mRNA translation, at least in part through mechanisms involving its 5′- and 3′-untranslated regions. In addition, the rate of leptin secretion from preformed stores in response to hormonal cues is also regulated. Insulin stimulates, and adrenergic agonists inhibit, leptin secretion, and this likely contributes to variations in the magnitude of nutrition-related leptin excursions and oscillations. Overall, the study of leptin production has contributed to a deepening understanding of leptin biology and, more broadly, to our understanding of the cellular and molecular mechanisms by which the adipocyte integrates hormonal and nutrient signals to regulate adipokine production.


Author(s):  
Pedro G Nachtigall ◽  
Andre Y Kashiwabara ◽  
Alan M Durham

Abstract Motivation Characterization of the coding sequences (CDSs) is an essential step in transcriptome annotation. Incorrect identification of CDSs can lead to the prediction of non-existent proteins that can eventually compromise knowledge if databases are populated with similar incorrect predictions made in different genomes. Also, the correct identification of CDSs is important for the characterization of the untranslated regions (UTRs), which are known to be important regulators of the mRNA translation process. Considering this, we present CodAn (Coding sequence Annotator), a new approach to predict confident CDS and UTR regions in full or partial transcriptome sequences in eukaryote species. Results Our analysis revealed that CodAn performs confident predictions on full-length and partial transcripts with the strand sense of the CDS known or unknown. The comparative analysis showed that CodAn presents better overall performance than other approaches, mainly when considering the correct identification of the full CDS (i.e. correct identification of the start and stop codons). In this sense, CodAn is the best tool to be used in projects involving transcriptomic data. Availability CodAn is freely available at https://github.com/pedronachtigall/CodAn. Contact [email protected] Supplementary information Supplementary data are available at Briefings in Bioinformatics online.


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