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https://www.readbyqxmd.com/read/29728453/boron-dependent-translational-suppression-of-the-borate-exporter-bor1-contributes-to-the-avoidance-of-boron-toxicity
#1
Izumi Aibara, Tatsuya Hirai, Koji Kasai, Junpei Takano, Hitoshi Onouchi, Satoshi Naito, Toru Fujiwara, Kyoko Miwa
Boron (B) is an essential element for plants; however, as high B concentrations are toxic, B transport must be tightly regulated. BOR1 is a borate exporter in Arabidopsis thaliana that facilitates B translocation into shoots under B deficiency conditions. When the B supply is sufficient, BOR1 expression is downregulated by selective degradation of BOR1 protein, while additional BOR1 regulatory mechanisms are proposed to exist. In this study, we identified a novel B-dependent BOR1 translational suppression mechanism...
May 4, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29708496/reduced-expression-of-c-ebp%C3%AE-lip-extends-health-and-lifespan-in-mice
#2
Christine Müller, Laura M Zidek, Tobias Ackermann, Tristan de Jong, Peng Liu, Verena Kliche, Mohamad Amr Zaini, Gertrud Kortman, Liesbeth Harkema, Dineke S Verbeek, Jan P Tuckermann, Julia von Maltzahn, Alain de Bruin, Victor Guryev, Zhao-Qi Wang, Cornelis F Calkhoven
Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb -mRNA. Here we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice...
April 30, 2018: ELife
https://www.readbyqxmd.com/read/29692761/ribosome-shunting-polycistronic-translation-and-evasion-of-antiviral-defenses-in-plant-pararetroviruses-and-beyond
#3
REVIEW
Mikhail M Pooggin, Lyubov A Ryabova
Viruses have compact genomes and usually translate more than one protein from polycistronic RNAs using leaky scanning, frameshifting, stop codon suppression or reinitiation mechanisms. Viral (pre-)genomic RNAs often contain long 5'-leader sequences with short upstream open reading frames (uORFs) and secondary structure elements, which control both translation initiation and replication. In plants, viral RNA and DNA are targeted by RNA interference (RNAi) generating small RNAs that silence viral gene expression, while viral proteins are recognized by innate immunity and autophagy that restrict viral infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29684192/the-exon-intron-gene-structure-upstream-of-the-initiation-codon-predicts-translation-efficiency
#4
Chun Shen Lim, Samuel J T Wardell, Torsten Kleffmann, Chris M Brown
Introns in mRNA leaders are common in complex eukaryotes, but often overlooked. These introns are spliced out before translation, leaving exon-exon junctions in the mRNA leaders (leader EEJs). Our multi-omic approach shows that the number of leader EEJs inversely correlates with the main protein translation, as does the number of upstream open reading frames (uORFs). Across the five species studied, the lowest levels of translation were observed for mRNAs with both leader EEJs and uORFs (29%). This class of mRNAs also have ribosome footprints on uORFs, with strong triplet periodicity indicating uORF translation...
April 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29562350/a-comprehensive-catalog-of-predicted-functional-upstream-open-reading-frames-in-humans
#5
Patrick McGillivray, Russell Ault, Mayur Pawashe, Robert Kitchen, Suganthi Balasubramanian, Mark Gerstein
Upstream open reading frames (uORFs) latent in mRNA transcripts are thought to modify translation of coding sequences by altering ribosome activity. Not all uORFs are thought to be active in such a process. To estimate the impact of uORFs on the regulation of translation in humans, we first circumscribed the universe of all possible uORFs based on coding gene sequence motifs and identified 1.3 million unique uORFs. To determine which of these are likely to be biologically relevant, we built a simple Bayesian classifier using 89 attributes of uORFs labeled as active in ribosome profiling experiments...
March 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29554358/an-upstream-open-reading-frame-uorf-signals-for-cellular-localization-of-the-virulence-factor-implicated-in-pregnancy-associated-malaria
#6
Yair Fastman, Shany Assaraf, Miriam Rose, Elad Milrot, Katherine Basore, B Sivanandam Arasu, Sanjay A Desai, Michael Elbaum, Ron Dzikowski
Plasmodium falciparum, the causative agent of the deadliest form of human malaria, alternates expression of variable antigens, encoded by members of a multi-copy gene family named var. In var2csa, the var gene implicated in pregnancy-associated malaria, translational repression is regulated by a unique upstream open reading frame (uORF) found only in its 5' UTR. Here, we report that this translated uORF significantly alters both transcription and posttranslational protein trafficking. The parasite can alter a protein's destination without any modifications to the protein itself, but instead by an element within the 5' UTR of the transcript...
March 15, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29529302/translational-profiling-of-b-cells-infected-with-the-epstein-barr-virus-reveals-5-leader-ribosome-recruitment-through-upstream-open-reading-frames
#7
Maja Bencun, Olaf Klinke, Agnes Hotz-Wagenblatt, Severina Klaus, Ming-Han Tsai, Remy Poirey, Henri-Jacques Delecluse
The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by monosomes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29452634/m-6-a-and-eif2%C3%AE-%C3%A2-team-up-to-tackle-atf4-translation-during-stress
#8
Emily Nicole Powers, Gloria Ann Brar
While m6 A modification of mRNAs is now known to be widespread, the cellular roles of this modification remain largely mysterious. In this issue of Molecular Cell, Zhou et al. (2018) show that m6 A modification unexpectedly contributes to the established uORF- and eIF2α-ⓟ-dependent mechanism of ATF4 translational regulation in response to stress.
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29446201/transposable-elements-shape-the-human-proteome-landscape-via-formation-of-cis-acting-upstream-open-reading-frames
#9
Shohei Kitano, Hikaru Kurasawa, Yasunori Aizawa
Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis-acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed "transposon-derived upstream ATGs" or TuATGs...
April 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29440070/role-of-eif2%C3%AE-kinases-in-translational-control-and-adaptation-to-cellular-stress
#10
Ronald C Wek
A central mechanism regulating translation initiation in response to environmental stress involves phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α causes inhibition of global translation, which conserves energy and facilitates reprogramming of gene expression and signaling pathways that help to restore protein homeostasis. Coincident with repression of protein synthesis, many gene transcripts involved in the stress response are not affected or are even preferentially translated in response to increased eIF2α phosphorylation by mechanisms involving upstream open reading frames (uORFs)...
February 12, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29432178/general-amino-acid-control-in-fission-yeast-is-regulated-by-a-nonconserved-transcription-factor-with-functions-analogous-to-gcn4-atf4
#11
Caia D S Duncan, María Rodríguez-López, Phil Ruis, Jürg Bähler, Juan Mata
Eukaryotes respond to amino acid starvation by enhancing the translation of mRNAs encoding b-ZIP family transcription factors ( GCN4 in Saccharomyces cerevisiae and ATF4 in mammals), which launch transcriptional programs to counter this stress. This pathway involves phosphorylation of the eIF2 translation factor by Gcn2-protein kinases and is regulated by upstream ORFs (uORFs) in the GCN4 / ATF4 5' leaders. Here, we present evidence that the transcription factors that mediate this response are not evolutionarily conserved...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29402903/loss-of-function-uorf-mutations-in-human-malignancies
#12
Julia Schulz, Nancy Mah, Martin Neuenschwander, Tabea Kischka, Richard Ratei, Peter M Schlag, Esmeralda Castaños-Vélez, Iduna Fichtner, Per-Ulf Tunn, Carsten Denkert, Oliver Klaas, Wolfgang E Berdel, Jens P von Kries, Wojciech Makalowski, Miguel A Andrade-Navarro, Achim Leutz, Klaus Wethmar
Ribosome profiling revealed widespread translational activity at upstream open reading frames (uORFs) and validated uORF-mediated translational control as a commonly repressive mechanism of gene expression. Translational activation of proto-oncogenes through loss-of-uORF mutations has been demonstrated, yet a systematic search for cancer-associated genetic alterations in uORFs is lacking. Here, we applied a PCR-based, multiplex identifier-tagged deep sequencing approach to screen 404 uORF translation initiation sites of 83 human tyrosine kinases and 49 other proto-oncogenes in 308 human malignancies...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323119/cug-initiation-and-frameshifting-enable-production-of-dipeptide-repeat-proteins-from-als-ftd-c9orf72-transcripts
#13
Ricardos Tabet, Laure Schaeffer, Fernande Freyermuth, Melanie Jambeau, Michael Workman, Chao-Zong Lee, Chun-Chia Lin, Jie Jiang, Karen Jansen-West, Hussein Abou-Hamdan, Laurent Désaubry, Tania Gendron, Leonard Petrucelli, Franck Martin, Clotilde Lagier-Tourenne
Expansion of G4 C2 repeats in the C9ORF72 gene is the most prevalent inherited form of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded transcripts undergo repeat-associated non-AUG (RAN) translation producing dipeptide repeat proteins from all reading frames. We determined cis-factors and trans-factors influencing translation of the human C9ORF72 transcripts. G4 C2 translation operates through a 5'-3' cap-dependent scanning mechanism, requiring a CUG codon located upstream of the repeats and an initiator Met-tRNAMet i ...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29281982/polyamines-in-the-life-of-arabidopsis-profiling-the-expression-of-s-adenosylmethionine-decarboxylase-samdc-gene-family-during-its-life-cycle
#14
Rajtilak Majumdar, Lin Shao, Swathi A Turlapati, Subhash C Minocha
BACKGROUND: Arabidopsis has 5 paralogs of the S-adenosylmethionine decarboxylase (SAMDC) gene. Neither their specific role in development nor the role of positive/purifying selection in genetic divergence of this gene family is known. While some data are available on organ-specific expression of AtSAMDC1, AtSAMDC2, AtSAMDC3 and AtSAMDC4, not much is known about their promoters including AtSAMDC5, which is believed to be non-functional. RESULTS: (1) Phylogenetic analysis of the five AtSAMDC genes shows similar divergence pattern for promoters and coding sequences (CDSs), whereas, genetic divergence of 5'UTRs and 3'UTRs was independent of the promoters and CDSs; (2) while AtSAMDC1 and AtSAMDC4 promoters exhibit high activity (constitutive in the former), promoter activities of AtSAMDC2, AtSAMDC3 and AtSAMDC5 are moderate to low in seedlings (depending upon translational or transcriptional fusions), and are localized mainly in the vascular tissues and reproductive organs in mature plants; (3) based on promoter activity, it appears that AtSAMDC5 is both transcriptionally and translationally active, but based on it's coding sequence it seems to produce a non-functional protein; (4) though 5'-UTR based regulation of AtSAMDC expression through upstream open reading frames (uORFs) in the 5'UTR is well known, no such uORFs are present in AtSAMDC4 and AtSAMDC5; (5) the promoter regions of all five AtSAMDC genes contain common stress-responsive elements and hormone-responsive elements; (6) at the organ level, the activity of AtSAMDC enzyme does not correlate with the expression of specific AtSAMDC genes or with the contents of spermidine and spermine...
December 28, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29281028/please-do-not-recycle-translation-reinitiation-in-microbes-and-higher-eukaryotes
#15
Stanislava Gunišová, Vladislava Hronová, Mahabub Pasha Mohammad, Alan G Hinnebusch, Leoš Shivaya Valášek
Protein production must be strictly controlled at its beginning and end to synthesize a polypeptide that faithfully copies genetic information carried in the encoding mRNA. In contrast to viruses and prokaryotes, the majority of mRNAs in eukaryotes contain only one coding sequence, resulting in production of a single protein. There are, however, many exceptional mRNAs that either carry short open reading frames upstream of the main coding sequence (uORFs) or even contain multiple long ORFs. A wide variety of mechanisms have evolved in microbes and higher eukaryotes to prevent recycling of some or all translational components upon termination of the first translated ORF in such mRNAs and thereby enable subsequent translation of the next uORF or downstream coding sequence...
March 1, 2018: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/29220654/a-unique-isr-program-determines-cellular-responses-to-chronic-stress
#16
Bo-Jhih Guan, Vincent van Hoef, Raul Jobava, Orna Elroy-Stein, Leos S Valasek, Marie Cargnello, Xing-Huang Gao, Dawid Krokowski, William C Merrick, Scot R Kimball, Anton A Komar, Antonis E Koromilas, Anthony Wynshaw-Boris, Ivan Topisirovic, Ola Larsson, Maria Hatzoglou
The integrated stress response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29162641/discovery-of-noncanonical-translation-initiation-sites-through-mass-spectrometric-analysis-of-protein-n-termini
#17
Chan Hyun Na, Mustafa A Barbhuiya, Min-Sik Kim, Steven Verbruggen, Stephen M Eacker, Olga Pletnikova, Juan C Troncoso, Marc K Halushka, Gerben Menschaert, Christopher M Overall, Akhilesh Pandey
Translation initiation generally occurs at AUG codons in eukaryotes, although it has been shown that non-AUG or noncanonical translation initiation can also occur. However, the evidence for noncanonical translation initiation sites (TISs) is largely indirect and based on ribosome profiling (Ribo-seq) studies. Here, using a strategy specifically designed to enrich N termini of proteins, we demonstrate that many human proteins are translated at noncanonical TISs. The large majority of TISs that mapped to 5' untranslated regions were noncanonical and led to N-terminal extension of annotated proteins or translation of upstream small open reading frames (uORF)...
January 2018: Genome Research
https://www.readbyqxmd.com/read/29114030/near-cognate-codons-contribute-complexity-to-translation-regulation
#18
N Louise Glass
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...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29109288/an-rna-structure-mediated-posttranscriptional-model-of-human-%C3%AE-1-antitrypsin-expression
#19
Meredith Corley, Amanda Solem, Gabriela Phillips, Lela Lackey, Benjamin Ziehr, Heather A Vincent, Anthony M Mustoe, Silvia B V Ramos, Kevin M Weeks, Nathaniel J Moorman, Alain Laederach
Chronic obstructive pulmonary disease (COPD) affects over 65 million individuals worldwide, where α-1-antitrypsin deficiency is a major genetic cause of the disease. The α-1-antitrypsin gene, SERPINA1 , expresses an exceptional number of mRNA isoforms generated entirely by alternative splicing in the 5'-untranslated region (5'-UTR). Although all SERPINA1 mRNAs encode exactly the same protein, expression levels of the individual mRNAs vary substantially in different human tissues. We hypothesize that these transcripts behave unequally due to a posttranscriptional regulatory program governed by their distinct 5'-UTRs and that this regulation ultimately determines α-1-antitrypsin expression...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29097404/deep-learning-of-the-regulatory-grammar-of-yeast-5-untranslated-regions-from-500-000-random-sequences
#20
Josh T Cuperus, Benjamin Groves, Anna Kuchina, Alexander B Rosenberg, Nebojsa Jojic, Stanley Fields, Georg Seelig
Our ability to predict protein expression from DNA sequence alone remains poor, reflecting our limited understanding of cis -regulatory grammar and hampering the design of engineered genes for synthetic biology applications. Here, we generate a model that predicts the protein expression of the 5' untranslated region (UTR) of mRNAs in the yeast Saccharomyces cerevisiae. We constructed a library of half a million 50-nucleotide-long random 5' UTRs and assayed their activity in a massively parallel growth selection experiment...
December 2017: Genome Research
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