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https://www.readbyqxmd.com/read/29153836/post-transcriptional-regulation-of-de-novo-lipogenesis-by-mtorc1-s6k1-srpk2-signaling
#1
Gina Lee, Yuxiang Zheng, Sungyun Cho, Cholsoon Jang, Christina England, Jamie M Dempsey, Yonghao Yu, Xiaolei Liu, Long He, Paola M Cavaliere, Andre Chavez, Erik Zhang, Meltem Isik, Anthony Couvillon, Noah E Dephoure, T Keith Blackwell, Jane J Yu, Joshua D Rabinowitz, Lewis C Cantley, John Blenis
mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling...
November 14, 2017: Cell
https://www.readbyqxmd.com/read/29146908/lrpprc-mediated-folding-of-the-mitochondrial-transcriptome
#2
Stefan J Siira, Henrik Spåhr, Anne-Marie J Shearwood, Benedetta Ruzzenente, Nils-Göran Larsson, Oliver Rackham, Aleksandra Filipovska
The expression of the compact mammalian mitochondrial genome requires transcription, RNA processing, translation and RNA decay, much like the more complex chromosomal systems, and here we use it as a model system to understand the fundamental aspects of gene expression. Here we combine RNase footprinting with PAR-CLIP at unprecedented depth to reveal the importance of RNA-protein interactions in dictating RNA folding within the mitochondrial transcriptome. We show that LRPPRC, in complex with its protein partner SLIRP, binds throughout the mitochondrial transcriptome, with a preference for mRNAs, and its loss affects the entire secondary structure and stability of the transcriptome...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146266/endophytism-or-saprophytism-decoding-the-lifestyle-transition-of-the-generalist-fungus-phomopsis-liquidambari
#3
Jun Zhou, Xin Li, Peng-Wei Huang, Chuan-Chao Dai
Filamentous ascomycete Phomopsis sp. are common inhabitants of natural ecosystems and, as saprophytes, are largely responsible for the destructive decay of litterfall, promoting the carbon and nitrogen cycles. Phomopsis liquidambari B3 can establish mutualistic symbiosis with a broad spectrum of crop plants. Colonizing dynamics observations and a growth promotion assay of rice and Arabidopsis thaliana revealed that the B3 colonization strategy is host-adapted and resulted in different growth promotions influenced by N availability...
January 2018: Microbiological Research
https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#4
Antoine Chaillon, Sara Gianella, Steven M Lada, Josué Perez-Santiago, Parris Jordan, Caroline Ignacio, Maile Karris, Douglas Richman, Sanjay R Mehta, Susan J Little, Joel O Wertheim, Davey M Smith
Residual viremia is common during antiretroviral therapy (ART), and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART Intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial, and followed for a median of 107 weeks. Participants started ART with (n=9) or without (n=9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29133129/hbsag-mrna-degradation-induced-by-dihydroquinolizinone-molecule-depends-on-hbv-posttranscriptional-regulatory-element
#5
Tianlun Zhou, Timothy Block, Fei Liu, Andrew S Kondratowicz, Liren Sun, Siddhartha Rawat, Jeffrey Branson, Fang Guo, Hongyan Liang, Lauren Bailey, Chris Moore, Xiaohe Wang, Andy Cuconatti, Min Gao, Amy C H Lee, Troy Harasym, Tim Chiu, Dimitar Gotchev, Bruce Dorsey, Rene Rijnbrand, Michael J Sofia
In pursuit of novel therapeutics targeting the hepatitis B virus (HBV) infection, we evaluated a dihydroquinolizinone compound (DHQ-1) that possessed nanomolar activities against the production of virion and surface protein (HBsAg) in tissue culture. This compound also showed broad HBV genotype coverage and was inactive against a panel of DNA and RNA viruses of other species. Oral administration of DHQ-1 in the AAV-HBV mouse model resulted in a strong reduction of serum HBsAg as soon as 4 days following the commencement of treatment...
November 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29130187/the-secret-life-of-rna-lessons-from-emerging-methodologies
#6
Caroline Medioni, Florence Besse
The last past decade has witnessed a revolution in our appreciation of transcriptome complexity and regulation. This remarkable expansion in our knowledge largely originates from the advent of high-throughput methodologies, and the consecutive discovery that up to 90% of eukaryotic genomes are transcribed, thus generating an unanticipated large range of noncoding RNAs (Hangauer et al., 15(4):112, 2014). Besides leading to the identification of new noncoding RNA species, transcriptome-wide studies have uncovered novel layers of posttranscriptional regulatory mechanisms controlling RNA processing, maturation or translation, and each contributing to the precise and dynamic regulation of gene expression...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29128743/the-suppression-of-premature-termination-codons-and-the-repair-of-splicing-mutations-in-cftr
#7
REVIEW
Yifat S Oren, Iwona M Pranke, Batsheva Kerem, Isabelle Sermet-Gaudelus
Premature termination codons (PTC) originate from nucleotide substitution introducing an in-frame PTC. They induce truncated, usually non-functional, proteins, degradation of the PTC containing transcripts by the nonsense-mediated decay (NMD) pathway and abnormal exon skipping. Readthrough compounds facilitate near cognate amino-acyl-tRNA incorporation, leading potentially to restoration of a functional full-length protein. Splicing mutations can lead to aberrantly spliced transcripts by creating a cryptic splice site or destroying a normal site...
November 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29120018/rna-metabolism-in-staphylococcus-aureus-virulence
#8
Patrick Linder, Joshua Armitano
The opportunistic pathogen Staphylococcus aureus encounters a variety of host defence systems depending on its localisation during colonisation in the nares, systemic infections within the body, or persistent infections within cells or embedded in biofilms. To respond rapidly to these different environments, this bacterium has evolved, in its longstanding interaction with animal and human hosts, a variety of mechanisms to fine-tune its gene expression. RNA metabolism, including transcription, processing, translation into proteins and RNA decay, is a central player in this response and might in the future be used to treat this feared pathogen...
November 9, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29118186/identification-of-phlebovirus-and-arenavirus-rna-sequences-that-stall-and-repress-the-exoribonuclease-xrn1
#9
Phillida A Charley, Carol J Wilusz, Jeffrey Wilusz
Regulated mRNA decay plays a vital role in determining both the level and quality of cellular gene expression. Viral RNAs must successfully evade this host RNA decay machinery to establish a productive infection. One way for RNA viruses to accomplish this is to target the cellular exoribonuclease XRN1, since this enzyme is accessible in the cytoplasm and plays a major role in mRNA decay. Members of the Flaviviridae use RNA structures in their 5' or 3' untranslated regions to stall and repress XRN1, effectively stabilizing viral RNAs while also causing significant dysregulation of host cell mRNA stability...
November 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29112072/an-advanced-blt-humanized-mouse-model-for-extended-hiv-1-cure-studies
#10
Kerry J Lavender, Craig Pace, Kathrin Sutter, Ronald J Messer, Dakota L Pouncey, Nathan W Cummins, Sekar Natesampillai, Jim Zheng, Joshua Goldsmith, Marek Widera, Erik S Van Dis, Katie Phillips, Brent Race, Ulf Dittmer, George Kukolj, Kim J Hasenkrug
OBJECTIVE: Although BLT-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: 1) Evaluate the GVHD-resistant C57BL/6 Rag2γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. 2) Determine whether TKO-BLT mice could be maintained on ART for extended periods of time...
November 2, 2017: AIDS
https://www.readbyqxmd.com/read/29106599/aspedia-a-comprehensive-encyclopedia-of-human-alternative-splicing
#11
Daejin Hyung, Jihyun Kim, Soo Young Cho, Charny Park
Alternative splicing confers the human genome complexity by increasing the diversity of expressed mRNAs. Hundreds or thousands of splicing regions have been identified through differential alternative splicing analysis of high-throughput datasets. However, it is hard to explain the functional impact of each splicing event. Protein domain formation and nonsense-mediated decay are considered the main functional features of splicing. However, other functional features such as miRNA target sites, phosphorylation sites and single-nucleotide variations are directly affected by alternative splicing and affect downstream function...
November 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29103173/a-role-for-the-mutagenic-dna-self-catalyzed-depurination-mechanism-in-the-evolution-of-7sl-derived-rnas
#12
Maxwell P Gold, Jacques R Fresco
The Alu element, the most prevalent SINE (short interspersed element) in the human genome, is one of the many RNA-encoding genes that evolved from the 7SL RNA gene. During analysis of the evolution of 7SL-derived RNAs, two distinct evolutionary intermediates capable of self-catalyzed DNA depurination (SDP) were identified. These SDP sequences spontaneously create apurinic sites that can result in increased mutagenesis due to their error-prone repair. This DNA self-depurination mechanism has been shown both in vitro and in vivo to lead to substitution and short frameshift mutations at a frequency that far exceeds their occurrence due to random errors in DNA replication...
October 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29100804/immunohistochemical-localization-of-exoribonucleases-dis3l2-and-xrn1-in-intranuclear-inclusion-body-disease
#13
Fumiaki Mori, Kunikazu Tanji, Yasuo Miki, Yasuko Toyoshima, Hidenao Sasaki, Mari Yoshida, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
mRNA turnover controls gene expression under various conditions in aging and neurodegenerative diseases. Polyglutamine (polyQ) diseases and intranuclear inclusion body disease (INIBD) are neurodegenerative diseases characterized by the formation of nuclear inclusions. These inclusions are immunopositive for several proteins associated with amyotrophic lateral sclerosis. In amyotrophic lateral sclerosis, the processing of RNA from gene transcription through degradation (RNA metabolism) has been reported to be altered...
October 31, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29100051/trick-or-treat-a-scary-good-new-approach-for-single-molecule-mrna-decay-analysis
#14
Joseph Russo, Jeffrey Wilusz
In this issue of Molecular Cell, Horvathova et al. (2017) have developed a powerful approach to single-molecule assessment of RNA decay in living cells by exploiting the ability of flavivirus RNA structural elements to trap XRN1 decay intermediates in dual-labeled reporter constructs.
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29099484/lin28b-and-mir-142-3p-regulate-neuronal-differentiation-by-modulating-staufen1-expression
#15
Younseo Oh, Jungyun Park, Jin-Il Kim, Mi-Yoon Chang, Sang-Hun Lee, Youl-Hee Cho, Jungwook Hwang
Staufen1 (STAU1) and Lin28B are RNA-binding proteins that are involved in neuronal differentiation as a function of post-transcriptional regulation. STAU1 triggers post-transcriptional regulation, including mRNA export, mRNA relocation, translation and mRNA decay. Lin28B also has multiple functions in miRNA biogenesis and the regulation of translation. Here, we examined the connection between STAU1 and Lin28B and found that Lin28B regulates the abundance of STAU1 mRNA via miRNA maturation. Decreases in the expression of both STAU1 and Lin28B were observed during neuronal differentiation...
November 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29099331/the-topological-train-ride-of-a-viral-long-non-coding-rna
#16
Joanna Sztuba-Solinska, Stuart F J Le Grice
As the notion of small molecule targeting of regulatory viral and cellular RNAs gathers momentum, understanding their structure, and variations thereof, in the appropriate biological context will play a critical role. This is especially true of the ∼1100-nt polyadenylated nuclear (PAN) long non-coding (lnc) RNA of Kaposi's sarcoma herpesvirus (KSHV), whose interaction with viral and cellular proteins is central to lytic infection. Nuclear accumulation of PAN RNA is mediated via a unique triple helical structure at its 3' terminus (within the expression and nuclear retention element, or ENE) which protects it from deadenylation-dependent decay...
November 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/29097662/translation-efficiency-is-a-determinant-of-the-magnitude-of-mirna-mediated-repression
#17
Kyle A Cottrell, Pawel Szczesny, Sergej Djuranovic
MicroRNAs are well known regulators of mRNA stability and translation. However, the magnitude of both translational repression and mRNA decay induced by miRNA binding varies greatly between miRNA targets. This can be the result of cis and trans factors that affect miRNA binding or action. We set out to address this issue by studying how various mRNA characteristics affect miRNA-mediated repression. Using a dual luciferase reporter system, we systematically analyzed the ability of selected mRNA elements to modulate miRNA-mediated repression...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079676/sex-biased-microrna-expression-in-mammals-and-birds-reveals-underlying-regulatory-mechanisms-and-a-role-in-dosage-compensation
#18
Maria Warnefors, Katharina Mössinger, Jean Halbert, Tania Studer, John L VandeBerg, Isa Lindgren, Amir Fallahshahroudi, Per Jensen, Henrik Kaessmann
Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes...
October 27, 2017: Genome Research
https://www.readbyqxmd.com/read/29078363/a-unique-surface-on-pat1-c-terminal-domain-directly-interacts-with-dcp2-decapping-enzyme-and-xrn1-5-3-mrna-exonuclease-in-yeast
#19
Clément Charenton, Claudine Gaudon-Plesse, Zaineb Fourati, Valerio Taverniti, Régis Back, Olga Kolesnikova, Bertrand Séraphin, Marc Graille
The Pat1 protein is a central player of eukaryotic mRNA decay that has also been implicated in translational control. It is commonly considered a central platform responsible for the recruitment of several RNA decay factors. We demonstrate here that a yeast-specific C-terminal region from Pat1 interacts with several short motifs, named helical leucine-rich motifs (HLMs), spread in the long C-terminal region of yeast Dcp2 decapping enzyme. Structures of Pat1-HLM complexes reveal the basis for HLM recognition by Pat1...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073135/the-gyf-domain-protein-psig1-dampens-the-induction-of-cell-death-during-plant-pathogen-interactions
#20
Hidenori Matsui, Yuko Nomura, Mayumi Egusa, Takahiro Hamada, Gang-Su Hyon, Hironori Kaminaka, Yuichiro Watanabe, Takashi Ueda, Marco Trujillo, Ken Shirasu, Hirofumi Nakagami
The induction of rapid cell death is an effective strategy for plants to restrict biotrophic and hemi-biotrophic pathogens at the infection site. However, activation of cell death comes at a high cost, as dead cells will no longer be available for defense responses nor general metabolic processes. In addition, necrotrophic pathogens that thrive on dead tissue, take advantage of cell death-triggering mechanisms. Mechanisms by which plants solve this conundrum remain described. Here, we identify PLANT SMY2-TYPE ILE-GYF DOMAIN-CONTAINING PROTEIN 1 (PSIG1) and show that PSIG1 helps to restrict cell death induction during pathogen infection...
October 2017: PLoS Genetics
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