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Translational genomics

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https://www.readbyqxmd.com/read/29166606/sumoylation-promotes-nuclear-import-and-stabilization-of-polo-like-kinase-1-to-support-its-mitotic-function
#1
Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29164808/a-universal-approach-to-correct-various-hbb-gene-mutations-in-human-stem-cells-for-gene-therapy-of-beta-thalassemia-and-sickle-cell-disease
#2
Liuhong Cai, Hao Bai, Vasiliki Mahairaki, Yongxing Gao, Chaoxia He, Yanfei Wen, You-Chuan Jin, You Wang, Rachel L Pan, Armaan Qasba, Zhaohui Ye, Linzhao Cheng
Beta-thalassemia is one of the most common recessive genetic diseases, caused by mutations in the HBB gene. Over 200 different types of mutations in the HBB gene containing three exons have been identified in patients with β-thalassemia (β-thal) whereas a homozygous mutation in exon 1 causes sickle cell disease (SCD). Novel therapeutic strategies to permanently correct the HBB mutation in stem cells that are able to expand and differentiate into erythrocytes producing corrected HBB proteins are highly desirable...
November 21, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29163371/cofactors-as-metabolic-sensors-driving-cell-adaptation-in-physiology-and-disease
#3
REVIEW
Nabil Rabhi, Sarah Anissa Hannou, Philippe Froguel, Jean-Sébastien Annicotte
Chromatin architectures and epigenetic fingerprint regulation are fundamental for genetically determined biological processes. Chemical modifications of the chromatin template sensitize the genome to intracellular metabolism changes to set up diverse functional adaptive states. Accumulated evidence suggests that the action of epigenetic modifiers is sensitive to changes in dietary components and cellular metabolism intermediates, linking nutrition and energy metabolism to gene expression plasticity. Histone posttranslational modifications create a code that acts as a metabolic sensor, translating changes in metabolism into stable gene expression patterns...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29162923/overexpression-of-suppressive-micrornas-mir-30a-and-mir-200c-are-associated-with-improved-survival-of-breast-cancer-patients
#4
Tsutomu Kawaguchi, Li Yan, Qianya Qi, Xuan Peng, Emmanuel M Gabriel, Jessica Young, Song Liu, Kazuaki Takabe
Some microRNAs (miRNAs) are known to suppress breast cancer. However, whether the expressions of these tumor suppressive miRNAs translate to patient survival were not investigated in large cohort. Nine miRNAs (miR-30a, miR-30c, miR-31, miR-126, miR-140, miR-146b, miR-200c, miR-206, and miR-335) known to be tumor suppressive miRNAs in breast cancer were investigated in Genomic Data Common data portal miRNA-Seq dataset and The Cancer Genome Atlas (TCGA) (n = 1052). Of the 9 miRNAs, miR-30a, miR-30c, miR-126, miR-140, miR-206, and miR-335 were found to have significantly lower expression in breast cancer tissues compared to paired normal breast tissue...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162165/epigenetic-correlates-of-neonatal-contact-in-humans
#5
Sarah R Moore, Lisa M McEwen, Jill Quirt, Alex Morin, Sarah M Mah, Ronald G Barr, W Thomas Boyce, Michael S Kobor
Animal models of early postnatal mother-infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4-5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29161365/genome-scale-analysis-ofescherichia-coliwith-a-comprehensive-prokaryotic-sequence-based-biophysical-model-of-translation-initiation-and-elongation
#6
Gilad Shaham, Tamir Tuller
Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation...
November 17, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29161012/top-down-proteomics-ready-for-prime-time
#7
Bifan Chen, Kyle A Brown, Ziqing Lin, Ying Ge
In the post-genomics era, the study of proteins is critical for understanding cellular functions at the molecular level.1-5 Beyond the genetic code, the human proteome is greatly diversified by various genetic variations, alternative splicing of RNA transcripts, and post-translational modifi-cations (PTMs).6,7 In 2013, the term "proteoform" was designated to describe "all of the different molecular forms in which the protein product of a single gene can be found",6 clearing up the confusion in nomenclature and joining research efforts to develop methodologies for pro-teoform characterization...
November 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29159494/the-nucleocapsid-protein-of-hantaviruses-much-more-than-a-genome-wrapping-protein
#8
REVIEW
Monika Reuter, Detlev H Krüger
The nucleocapsid (N) protein of hantaviruses represents an impressive example of a viral multifunctional protein. It encompasses properties as diverse as genome packaging, RNA chaperoning, intracellular protein transport, DNA degradation, intervention in host translation, and restricting host immune responses. These functions all rely on the capability of N to interact with RNA and other viral and cellular proteins. We have compiled data on the N protein of different hantavirus species together with information of the recently published three-dimensional structural data of the protein...
November 20, 2017: Virus Genes
https://www.readbyqxmd.com/read/29159200/analyzing-the-genotoxicity-of-retroviral-vectors-in-hematopoietic-cell-gene-therapy
#9
REVIEW
Luca Biasco, Michael Rothe, Hildegard Büning, Axel Schambach
Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29158982/genome-wide-in-silico-identification-of-membrane-bound-transcription-factors-in-plant-species
#10
Shixiang Yao, Lili Deng, Kaifang Zeng
Membrane-bound transcription factors (MTFs) are located in cellular membranes due to their transmembrane domains. In plants, proteolytic processing is considered to be the main mechanism for MTF activation, which ensures the liberation of MTFs from membranes and further their translocation into the nucleus to regulate gene expression; this process skips both the transcriptional and translational stages, and thus it guarantees the prompt responses of plants to various stimuli. Currently, information concerning plant MTFs is limited to model organisms, including Arabidopsis thaliana and Oryza sativa, and little is known in other plant species at the genome level...
2017: PeerJ
https://www.readbyqxmd.com/read/29158838/crispr-genome-engineering-for-human-pluripotent-stem-cell-research
#11
REVIEW
Somali Chaterji, Eun Hyun Ahn, Deok-Ho Kim
The emergence of targeted and efficient genome editing technologies, such as repurposed bacterial programmable nucleases (e.g., CRISPR-Cas systems), has abetted the development of cell engineering approaches. Lessons learned from the development of RNA-interference (RNA-i) therapies can spur the translation of genome editing, such as those enabling the translation of human pluripotent stem cell engineering. In this review, we discuss the opportunities and the challenges of repurposing bacterial nucleases for genome editing, while appreciating their roles, primarily at the epigenomic granularity...
2017: Theranostics
https://www.readbyqxmd.com/read/29158557/mir-29b-antagonizes-the-pro-inflammatory-tumor-promoting-activity-of-multiple-myeloma-educated-dendritic-cells
#12
C Botta, M Cucè, M R Pitari, D Caracciolo, A Gullà, E Morelli, C Riillo, L Biamonte, M E G Cantafio, R Prabhala, C Mignogna, A Di Vito, E Altomare, N Amodio, M T Di Martino, P Correale, M Rossi, A Giordano, N C Munshi, P Tagliaferri, P Tassone
Dendritic cells (DCs) play a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their miRNA network. By analyzing 6 different miRNA-profiling datasets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients...
November 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29158530/mrnas-containing-nmd-competent-premature-termination-codons-are-stabilized-and-translated-under-upf1-depletion
#13
Won Kyu Kim, SeongJu Yun, Yujin Kwon, Kwon Tae You, Nara Shin, Jiyoon Kim, Hoguen Kim
mRNAs containing premature termination codons (PTCs) are rapidly degraded through nonsense-mediated mRNA decay (NMD). However, some PTC-containing mRNAs evade NMD, and might generate mutant proteins responsible for various diseases, including cancers. Using PTC-containing human genomic β-globin constructs, we show that a fraction (~30%) of PTC-containing mRNAs expressed from NMD-competent PTC-containing constructs were as stable as their PTC-free counterparts in a steady state. These PTC-containing mRNAs were monosome-enriched and rarely contributed to expression of mutant proteins...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158339/genome-wide-mapping-of-decay-factor-mrna-interactions-in-yeast-identifies-nutrient-responsive-transcripts-as-targets-of-the-deadenylase-ccr4
#14
Jason E Miller, Liye Zhang, Haoyang Jiang, Yunfei Li, B Franklin Pugh, Joseph C Reese
The Ccr4-Not complex is a major regulator of stress responses that controls gene expression at multiple levels, from transcription to mRNA decay. Ccr4, a core subunit of the complex, is the main cytoplasmic deadenylase in Saccharomyces cerevisiae, however its mRNA targets have not been mapped on a genome-wide scale. Here we describe a genome-wide approach, RNA immunoprecipitation-high throughput sequencing (RIP-seq), to identify the RNAs bound to Ccr4, and two proteins that associate with it, Dhh1 and Puf5...
November 20, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29157358/rng105-caprin1-an-rna-granule-protein-for-dendritic-mrna-localization-is-essential-for-long-term-memory-formation
#15
Kei Nakayama, Rie Ohashi, Yo Shinoda, Maya Yamazaki, Manabu Abe, Akihiro Fujikawa, Shuji Shigenobu, Akira Futatsugi, Masaharu Noda, Katsuhiko Mikoshiba, Teiichi Furuichi, Kenji Sakimura, Nobuyuki Shiina
Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks...
November 21, 2017: ELife
https://www.readbyqxmd.com/read/29155639/when-machines-think-radiology-s-next-frontier
#16
Keith J Dreyer, J Raymond Geis
Artificial intelligence (AI), machine learning, and deep learning are terms now seen frequently, all of which refer to computer algorithms that change as they are exposed to more data. Many of these algorithms are surprisingly good at recognizing objects in images. The combination of large amounts of machine-consumable digital data, increased and cheaper computing power, and increasingly sophisticated statistical models combine to enable machines to find patterns in data in ways that are not only cost-effective but also potentially beyond humans' abilities...
December 2017: Radiology
https://www.readbyqxmd.com/read/29155138/hpv16-e5-is-produced-from-an-hpv16-early-mrna-spliced-from-sd226-to-sa3358
#17
Kersti Nilsson, Christopher Norberg, Ann-Kristin Mossberg, Stefan Schwartz
The HPV16 E5 open reading frame (ORF) is present on the majority of all alternatively spliced HPV16 mRNAs, but it is currently unknown how well it is translated into E5 protein. To identify HPV16 mRNAs that are efficiently translated into E5, we have generated cDNA plasmids expressing individual, alternatively spliced HPV16 mRNAs with the potential to produce E5. By replacing the E5 ORF with sLuc, we could quantitate sLuc and determine how well each cDNA was translated. Our results showed that the upstream E1 and E7 AUGs inhibited translation of the E5 ORF and revealed that only one HPV16 mRNA produced high levels of E5...
November 16, 2017: Virus Research
https://www.readbyqxmd.com/read/29154288/patterns-of-calcium-signaling-a-link-between-chronic-emotions-and-cancer
#18
Massimo Pregnolato, Giuseppe Damiani, Alfredo Pereira
Intra and inter-cellular calcium signaling is present in all types of cells and body tissues. In the human brain, calcium currents and waves are related to mental activities, including emotions. We present a theoretical interpretation of these phenomena suggesting their involvement in chronic emotional patterns and in the pathology of cancer. Recent developments on biophysics, translational biology and psychoneuroendocrinoimmunology (PNEI) can support explanatory hypotheses about the link between emotional stresses and the origin and development of different types of tumor cells...
November 13, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/29154141/novel-genes-associated-with-amyotrophic-lateral-sclerosis-diagnostic-and-clinical-implications
#19
REVIEW
Ruth Chia, Adriano Chiò, Bryan J Traynor
BACKGROUND: The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS...
November 16, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29151450/identification-and-expression-analysis-of-cdna-encoding-insulin-like-growth-factor-2-in-horses
#20
Kohta Kikuchi, Keisuke Sasaki, Hiroki Akizawa, Hayato Tsukahara, Hanako Bai, Masashi Takahashi, Yasuo Nambo, Hiroshi Hata, Manabu Kawahara
Insulin-like growth factor 2 (IGF2) is responsible for a broad range of physiological processes during fetal development and adulthood, but genomic analyses of IGF2 containing the 5'- and 3'-untranslated regions (UTRs) in equines have been limited. In this study, we characterized the IGF2 mRNA containing the UTRs, and determined its expression pattern in the fetal tissues of horses. The complete equine IGF2 mRNA sequence harboring another exon approximately 2.8 kb upstream from the canonical transcription start site was identified as a new transcript variant...
November 17, 2017: Journal of Reproduction and Development
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