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https://www.readbyqxmd.com/read/29162641/discovery-of-non-canonical-translation-initiation-sites-through-mass-spectrometric-analysis-of-protein-n-termini
#1
Chan Hyun Na, Mustafa Barbhuiya, Min-Sik Kim, Steven Verbruggen, Stephen Eacker, Olga Pletnikova, Juan Troncoso, Marc Halushka, Gerben Menschaert, Christopher Overall, Akhilesh Pandey
Translation initiation generally occurs at AUG codons in eukaryotes although it has been shown that non-AUG or non-canonical translation initiation can also occur. However, the evidence for non-canonical translation initiation sites (TISs) is largely indirect and based on ribosome profiling studies. Here, using a strategy specifically designed to enrich N-termini of proteins, we demonstrate that many human proteins are translated at non-canonical TISs. The large majority of TISs that mapped to 5' untranslated regions were non-canonical and led to N-terminal extension of annotated proteins or translation of upstream small open reading frames (uORF)...
November 21, 2017: Genome Research
https://www.readbyqxmd.com/read/29114030/near-cognate-codons-contribute-complexity-to-translation-regulation
#2
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
#3
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 6, 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
#4
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...
November 2, 2017: Genome Research
https://www.readbyqxmd.com/read/29080154/thermospermine-an-evolutionarily-ancient-but-functionally-new-compound-in-plants
#5
Taku Takahashi
Themospermine is a structural isomer of spermine and is present in some bacteria and most of plants. An Arabidopsis mutant, acaulis5 (acl5), that is defective in the biosynthesis of thermospermine displays excessive proliferation of xylem vessels with dwarfed growth. Recent studies using acl5 and its suppressor mutants that recover the growth without thermospermine have revealed that thermospermine plays a key role in the negative control of the proliferation of xylem vessels through enhancing translation of specific mRNAs that contain a conserved upstream open-reading-frame (uORF) in the 5' leader region...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29065505/kinases-of-eif2a-switch-translation-of-mrna-subset-during-neuronal-plasticity
#6
REVIEW
Ekaterina Chesnokova, Natalia Bal, Peter Kolosov
Compared to other types of cells, neurons express the largest number of diverse mRNAs, including neuron-specific ones. This mRNA diversity is required for neuronal function, memory storage, maintenance and retrieval. Regulation of translation in neurons is very complicated and involves various proteins. Some proteins, implementing translational control in other cell types, are used by neurons for synaptic plasticity. In this review, we discuss the neuron-specific activity of four kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), general control nonderepressible 2 kinase (GCN2), and heme-reguated eIF2α kinase (HRI), the substrate for which is α-subunit of eukaryotic initiation factor 2 (eIF2α)...
October 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29048540/long-read-sequencing-of-the-coffee-bean-transcriptome-reveals-the-diversity-of-full-length-transcripts
#7
Bing Cheng, Agnelo Furtado, Robert J Henry
Background: Polyploidization contributes to the complexity of gene expression resulting in numerous related but different transcripts. This study explored the transcriptome diversity and complexity of tetraploid Arabica coffee ( Coffea arabica ) bean. Long-read sequencing (LRS) by Pacbio Isoform sequencing (Iso-seq) was used to obtain full-length transcripts without the difficulty and uncertainty of assembly required for reads from short read technologies. The tetraploid transcriptome was annotated and compared with data from the sub-genome progenitors...
August 30, 2017: GigaScience
https://www.readbyqxmd.com/read/28971534/the-zap1-transcriptional-activator-negatively-regulates-translation-of-the-rtc4-mrna-through-the-use-of-alternative-5-transcript-leaders
#8
Amanda J Bird, Simon Labbé
The zinc-responsive transcription activator Zap1 plays a central role in zinc homeostasis in the budding yeast Saccharomyces cerevisiae. In zinc-deficient cells, Zap1 binds to zinc responsive elements in target gene promoters and activates gene expression. In most cases, Zap1-dependent gene activation results in increased levels of mRNAs and proteins. However, Zap1-dependent activation of RTC4 results in increased levels of the RTC4 mRNA and decreased levels of the Rtc4 protein. This atypical regulation results from Zap1-mediated changes in the transcriptional start site for RTC4 and the production of a RTC4 transcript with a longer 5' leader...
December 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28956754/a-uorf-represses-the-transcription-factor-athb1-in-aerial-tissues-to-avoid-a-deleterious-phenotype
#9
Pamela A Ribone, Matías Capella, Agustín L Arce, Raquel L Chan
AtHB1 is an Arabidopsis (Arabidopsis thaliana) homeodomain-leucine zipper transcription factor that participates in hypocotyl elongation under short-day conditions. Here, we show that its expression is posttranscriptionally regulated by an upstream open reading frame (uORF) located in its 5' untranslated region. This uORF encodes a highly conserved peptide (CPuORF) that is present in varied monocot and dicot species. The Arabidopsis uORF and its maize (Zea mays) homolog repressed the translation of the main open reading frame in cis, independent of the sequence of the latter...
November 2017: Plant Physiology
https://www.readbyqxmd.com/read/28826393/ribosome-profiling-reveals-translational-regulation-of-mammalian-cells-in-response-to-hypoxic-stress
#10
Zhiwen Jiang, Jiaqi Yang, Aimei Dai, Yuming Wang, Wei Li, Zhi Xie
BACKGROUND: Retinal pigment epithelium (RPE) cells transfer oxygen and nutrients from choroid to the neural retina. Reduced oxygen to RPE perturbs development and functions of blood vessels in retina. Previous efforts of genome-wide studies have been largely focused on transcriptional changes of cells in response to hypoxia. Recently developed ribosome profiling provides an opportunity to study genome-wide translational changes. To gain systemic insights into the transcriptional and translational regulation of cellular in response to hypoxic stress, we used simultaneous RNA sequencing and ribosome profiling on an RPE cells line, ARPE-19, under hypoxia condition...
August 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28745933/does-eif3-promote-reinitiation-after-translation-of-short-upstream-orfs-also-in-mammalian-cells
#11
Vladislava Hronová, Mahabub Pasha Mohammad, Susan Wagner, Josef Pánek, Stanislava Gunišová, Jakub Zeman, Kristýna Poncová, Leoš Shivaya Valášek
Reinitiation after translation of short upstream ORFs (uORFs) represents one of the means of regulation of gene expression on the mRNA-specific level in response to changing environmental conditions. Over the years it has been shown-mainly in budding yeast-that its efficiency depends on cis-acting features occurring in sequences flanking reinitiation-permissive uORFs, the nature of their coding sequences, as well as protein factors acting in trans. We earlier demonstrated that the first two uORFs from the reinitiation-regulated yeast GCN4 mRNA leader carry specific structural elements in their 5' sequences that interact with the translation initiation factor eIF3 to prevent full ribosomal recycling post their translation...
July 26, 2017: RNA Biology
https://www.readbyqxmd.com/read/28739310/identification-of-new-tsga10-transcript-variants-in-human-testis-with-conserved-regulatory-rna-elements-in-5-untranslated-region-and-distinct-expression-in-breast-cancer
#12
Pouya Salehipour, Mahsa Nematzadeh, Maryam Beigom Mobasheri, Mandana Afsharpad, Kamran Mansouri, Mohammad Hossein Modarressi
Testis specific gene antigen 10 (TSGA10) is a cancer testis antigen involved in the process of spermatogenesis. TSGA10 could also play an important role in the inhibition of angiogenesis by preventing nuclear localization of HIF-1α. Although it has been shown that TSGA10 messenger RNA (mRNA) is mainly expressed in testis and some tumors, the transcription pattern and regulatory mechanisms of this gene remain largely unknown. Here, we report that human TSGA10 comprises at least 22 exons and generates four different transcript variants...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28659957/auxin-signaling-in-regulation-of-plant-translation-reinitiation
#13
REVIEW
Mikhail Schepetilnikov, Lyubov A Ryabova
The mRNA translation machinery directs protein production, and thus cell growth, according to prevailing cellular and environmental conditions. The target of rapamycin (TOR) signaling pathway-a major growth-related pathway-plays a pivotal role in optimizing protein synthesis in mammals, while its deregulation triggers uncontrolled cell proliferation and the development of severe diseases. In plants, several signaling pathways sensitive to environmental changes, hormones, and pathogens have been implicated in post-transcriptional control, and thus far phytohormones have attracted most attention as TOR upstream regulators in plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28655822/translation-initiation-from-conserved-non-aug-codons-provides-additional-layers-of-regulation-and-coding-capacity
#14
Ivaylo P Ivanov, Jiajie Wei, Stephen Z Caster, Kristina M Smith, Audrey M Michel, Ying Zhang, Andrew E Firth, Michael Freitag, Jay C Dunlap, Deborah Bell-Pedersen, John F Atkins, Matthew S Sachs
Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation...
June 27, 2017: MBio
https://www.readbyqxmd.com/read/28639196/specific-increase-of-protein-levels-by-enhancing-translation-using-antisense-oligonucleotides-targeting-upstream-open-frames
#15
Xue-Hai Liang, Wen Shen, Stanley T Crooke
A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28637336/identification-of-arabidopsis-thaliana-upstream-open-reading-frames-encoding-peptide-sequences-that-cause-ribosomal-arrest
#16
Noriya Hayashi, Shun Sasaki, Hiro Takahashi, Yui Yamashita, Satoshi Naito, Hitoshi Onouchi
Specific sequences of certain nascent peptides cause programmed ribosomal arrest during mRNA translation to control gene expression. In eukaryotes, most known regulatory arrest peptides are encoded by upstream open reading frames (uORFs) present in the 5'-untranslated region of mRNAs. However, to date, a limited number of eukaryotic uORFs encoding arrest peptides have been reported. Here, we searched for arrest peptide-encoding uORFs among Arabidopsis thaliana uORFs with evolutionarily conserved peptide sequences...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28623304/identification-of-transcripts-with-short-stuorfs-as-targets-for-denr%C3%A2-mcts1-dependent-translation-in-human-cells
#17
Sibylle Schleich, Julieta M Acevedo, Katharina Clemm von Hohenberg, Aurelio A Teleman
The non-canonical initiation factors DENR and MCTS1 have been linked to cancer and autism. We recently showed in Drosophila that DENR and MCTS1 regulate translation re-initiation on transcripts containing upstream Open Reading Frames (uORFs) with strong Kozak sequences (stuORFs). Due to the medical relevance of DENR and MCTS1, it is worthwhile identifying the transcripts in human cells that depend on DENR and MCTS1 for their translation. We show here that in humans, as in Drosophila, transcripts with short stuORFs require DENR and MCTS1 for their optimal expression...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28541577/eif1-modulates-the-recognition-of-suboptimal-translation-initiation-sites-and-steers-gene-expression-via-uorfs
#18
Daria Fijalkowska, Steven Verbruggen, Elvis Ndah, Veronique Jonckheere, Gerben Menschaert, Petra Van Damme
Alternative translation initiation mechanisms such as leaky scanning and reinitiation potentiate the polycistronic nature of human transcripts. By allowing for reprogrammed translation, these mechanisms can mediate biological responses to stimuli. We combined proteomics with ribosome profiling and mRNA sequencing to identify the biological targets of translation control triggered by the eukaryotic translation initiation factor 1 (eIF1), a protein implicated in the stringency of start codon selection. We quantified expression changes of over 4000 proteins and 10 000 actively translated transcripts, leading to the identification of 245 transcripts undergoing translational control mediated by upstream open reading frames (uORFs) upon eIF1 deprivation...
July 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28514448/uorf-mediated-translation-allows-engineered-plant-disease-resistance-without-fitness-costs
#19
Guoyong Xu, Meng Yuan, Chaoren Ai, Lijing Liu, Edward Zhuang, Sargis Karapetyan, Shiping Wang, Xinnian Dong
Controlling plant disease has been a struggle for humankind since the advent of agriculture. Studies of plant immune mechanisms have led to strategies of engineering resistant crops through ectopic transcription of plants' own defence genes, such as the master immune regulatory gene NPR1 (ref. 1). However, enhanced resistance obtained through such strategies is often associated with substantial penalties to fitness, making the resulting products undesirable for agricultural applications. To remedy this problem, we sought more stringent mechanisms of expressing defence proteins...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28494858/mtorc1-balances-cellular-amino-acid-supply-with-demand-for-protein-synthesis-through-post-transcriptional-control-of-atf4
#20
Yeonwoo Park, Andrea Reyna-Neyra, Lucas Philippe, Carson C Thoreen
The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR...
May 9, 2017: Cell Reports
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