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upstream open reading frame

Sitapriya Moorthi, Tara Ann Burns, Gui-Qin Yu, Chiara Luberto
Bcr-Abl (break-point cluster region-abelson), the oncogenic trigger of chronic myelogenous leukemia (CML), has previously been shown to up-regulate the expression and activity of sphingomyelin synthase 1 (SMS1), which contributes to the proliferation of CML cells; however, the mechanism by which this increased expression of SMS1 is mediated remains unknown. In the current study, we show that Bcr-Abl enhances the expression of SMS1 via a 30-fold up-regulation of its transcription. Of most interest, the Bcr-Abl-regulated transcription of SMS1 is initiated from a novel transcription start site (TSS) that is just upstream of the open reading frame...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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...
February 26, 2018: Nucleic Acids Research
Yi Xu, Ho Jung Ju, S DeBlasio, Elizabeth J Carino, R Johnson, M MacCoss, M Cilia Heck, W Allen Miller, S M Gray
Translational readthrough of the stop codon of the capsid protein (CP) open reading frame (ORF) is used by members of the Luteoviridae to produce their minor capsid protein as a readthrough protein (RTP). The elements regulating RTP expression are not well understood, but involve long-distance interactions between RNA domains. Using high-resolution mass spectrometry, glutamine and tyrosine were identified as the primary amino acids inserted at the stop codon of Potato leafroll virus (PLRV) CP ORF. We characterized the contributions of a cytidine-rich domain immediately downstream, and a branched stem-loop structure 600-700 nucleotides downstream of the CP stop codon...
March 7, 2018: Journal of Virology
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...
February 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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
Sarah M Hücker, Sonja Vanderhaeghen, Isabel Abellan-Schneyder, Romy Wecko, Svenja Simon, Siegfried Scherer, Klaus Neuhaus
BACKGROUND: Due to the DNA triplet code, it is possible that the sequences of two or more protein-coding genes overlap to a large degree. However, such non-trivial overlaps are usually excluded by genome annotation pipelines and, thus, only a few overlapping gene pairs have been described in bacteria. In contrast, transcriptome and translatome sequencing reveals many signals originated from the antisense strand of annotated genes, of which we analyzed an example gene pair in more detail...
February 12, 2018: BMC Evolutionary Biology
Dmitri E Andreev, Sergey E Dmitriev, Gary Loughran, Ilya M Terenin, Pavel V Baranov, Ivan N Shatsky
Eukaryotic cells evolved highly complex and accurate protein synthesis machinery that is finely tuned by various signaling pathways. Dysregulation of translation is a hallmark of many diseases, including cancer, and thus pharmacological approaches to modulate translation become very promising. While there has been much progress in our understanding of mammalian mRNA-specific translation control, surprisingly, relatively little is known about whether and how the protein components of the translation machinery shape translation of their own mRNAs...
February 4, 2018: Gene
Daichi Morimoto, Shigeko Kimura, Yoshihiko Sako, Takashi Yoshida
Microcystis aeruginosa forms massive blooms in eutrophic freshwaters, where it is constantly exposed to lytic cyanophages. Unlike other marine cyanobacteria, M. aeruginosa possess remarkably abundant and diverse potential antiviral defense genes. Interestingly, T4-like cyanophage Ma-LMM01, which is the sole cultured lytic cyanophage infecting M. aeruginosa, lacks the host-derived genes involved in maintaining host photosynthesis and directing host metabolism that are abundant in other marine cyanophages. Based on genomic comparisons with closely related cyanobacteria and their phages, Ma-LMM01 is predicted to employ a novel infection program that differs from that of other marine cyanophages...
2018: Frontiers in Microbiology
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
Nerea Irigoyen, Adam M Dinan, Ian Brierley, Andrew E Firth
BACKGROUND: The retrovirus murine leukemia virus (MuLV) has an 8.3 kb RNA genome with a simple 5'-gag-pol-env-3' architecture. Translation of the pol gene is dependent upon readthrough of the gag UAG stop codon; whereas the env gene is translated from spliced mRNA transcripts. Here, we report the first high resolution analysis of retrovirus gene expression through tandem ribosome profiling (RiboSeq) and RNA sequencing (RNASeq) of MuLV-infected cells. RESULTS: Ribosome profiling of MuLV-infected cells was performed, using the translational inhibitors harringtonine and cycloheximide to distinguish initiating and elongating ribosomes, respectively...
January 22, 2018: Retrovirology
Xia-Wei Jiang, Hong Cheng, Ying-Yi Huo, Lin Xu, Yue-Hong Wu, Wen-Hong Liu, Fang-Fang Tao, Xin-Jie Cui, Bei-Wen Zheng
Metallo-β-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used β-lactam-based antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by its success in rapidly disseminating worldwide since its first discovery. Here we report the biochemical and genetic characteristics of a novel MBL, ElBla2, from the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL...
January 16, 2018: Scientific Reports
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 G4C2 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. G4C2 translation operates through a 5'-3' cap-dependent scanning mechanism, requiring a CUG codon located upstream of the repeats and an initiator Met-tRNAMeti...
January 11, 2018: Nature Communications
John S Reece-Hoyes, Albertha J M Walhout
This protocol describes using the Gateway recombinatorial cloning system to simultaneously transfer a promoter and an open reading frame (ORF) from two different Entry clones into the same Destination vector using LR enzymes. A multisite cloning reaction transfers the inserts from multiple Entry clones into a single Destination vector. This type of recombination is much less efficient than transferring a single DNA fragment; however, the variety of Destination clones that can be generated in this manner is vast...
January 2, 2018: Cold Spring Harbor Protocols
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
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 has 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...
December 21, 2017: FEMS Microbiology Reviews
Bo Wang, Carrie Eckert, Pin-Ching Maness, Jianping Yu
Cyanobacteria, genetic models for photosynthesis research for decades, have recently become attractive hosts for producing renewable fuels and chemicals, owing to their genetic tractability, relatively fast growth, and their ability to utilize sunlight, fix carbon dioxide and, in some cases, fix nitrogen. Despite significant advances, there is still an urgent demand for synthetic biology tools in order to effectively manipulate genetic circuits in cyanobacteria. In this study, we have compared a total of 17 natural and chimeric promoters, focusing on expression of the ethylene-forming enzyme (EFE) in the cyanobacterium Synechocystis sp...
December 12, 2017: ACS Synthetic Biology
Musa A Hassan, Juan J Vasquez, Chew Guo-Liang, Markus Meissner, T Nicolai Siegel
BACKGROUND: The lytic cycle of the protozoan parasite Toxoplasma gondii, which involves a brief sojourn in the extracellular space, is characterized by defined transcriptional profiles. For an obligate intracellular parasite that is shielded from the cytosolic host immune factors by a parasitophorous vacuole, the brief entry into the extracellular space is likely to exert enormous stress. Due to its role in cellular stress response, we hypothesize that translational control plays an important role in regulating gene expression in Toxoplasma during the lytic cycle...
December 11, 2017: BMC Genomics
Douglas A Schober, Carrie H Croy, Cara L Ruble, Ran Tao, Christian C Felder
Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices...
2017: PloS One
Ming Li, Chunxia Ma, Haoyang Li, Jinxia Peng, Digang Zeng, Xiaohan Chen, Chaozheng Li
Antimicrobial peptides (AMPs) are the most important players in the innate immune system, providing a principal first-line of defense against the invading pathogens. Crustin, a type of whey acidic protein (WAP) domain-containing and cationic cysteine-rich AMP, can function in a protease inhibition or an effector molecule manner. In the present study, a new Crustin was cloned and identified from Pacific white shrimp Litopenaeus vannamei and designated as LvCrustinA. The full-length cDNA of LvCrustinA was 687 bp, with a 519 bp open reading frame (ORF) that encoded a peptide of 172 amino acids...
February 2018: Fish & Shellfish Immunology
Cristina Romero-López, Alfredo Berzal-Herranz
Viral genomes are complexly folded entities that carry all the information required for the infective cycle. The nucleotide sequence of the RNA virus genome encodes proteins and functional information contained in discrete, highly conserved structural units. These so-called functional RNA domains play essential roles in the progression of infection, which requires their preservation from one generation to the next. Numerous functional RNA domains exist in the genome of the hepatitis C virus (HCV). Among them, the 5BSL3...
2017: Frontiers in Microbiology
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