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Rna editing

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https://www.readbyqxmd.com/read/28535252/trypanosome-rna-editing-mediator-complex-proteins-have-distinct-functions-in-grna-utilization
#1
Rachel M Simpson, Andrew E Bruno, Runpu Chen, Kaylen Lott, Brianna L Tylec, Jonathan E Bard, Yijun Sun, Michael J Buck, Laurie K Read
Uridine insertion/deletion RNA editing is an essential process in kinetoplastid parasites whereby mitochondrial mRNAs are modified through the specific insertion and deletion of uridines to generate functional open reading frames, many of which encode components of the mitochondrial respiratory chain. The roles of numerous non-enzymatic editing factors have remained opaque given the limitations of conventional methods to interrogate the order and mechanism by which editing progresses and thus roles of individual proteins...
May 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28533980/mitochondrial-complex-i-deficiency-leads-to-the-retardation-of-early-embryonic-development-in-ndufs4-knockout-mice
#2
Mei Wang, Ya-Ping Huang, Han Wu, Ke Song, Cong Wan, A-Ni Chi, Ya-Mei Xiao, Xiao-Yang Zhao
BACKGROUND: The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS) in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO) mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown...
2017: PeerJ
https://www.readbyqxmd.com/read/28533408/rna-editing-of-slc22a3-drives-early-tumor-invasion-and-metastasis-in-familial-esophageal-cancer
#3
Li Fu, Yan-Ru Qin, Xiao-Yan Ming, Xian-Bo Zuo, Yu-Wen Diao, Li-Yi Zhang, Jiaoyu Ai, Bei-Lei Liu, Tu-Xiong Huang, Ting-Ting Cao, Bin-Bin Tan, Di Xiang, Chui-Mian Zeng, Jing Gong, Qiangfeng Zhang, Sui-Sui Dong, Juan Chen, Haibo Liu, Jian-Lin Wu, Robert Z Qi, Dan Xie, Li-Dong Wang, Xin-Yuan Guan
Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532996/histone-methyltransferase-g9a-promotes-liver-cancer-development-by-epigenetic-silencing-of-tumor-suppressor-gene-rarres3
#4
Lai Wei, David Kung-Chun Chiu, Felice Ho-Ching Tsang, Dicky Cheuk-Ting Law, Carol Lai-Hung Cheng, Sandy Leung-Kuen Au, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. Epigenetic deregulation is a common trait of human HCC. G9s is an important epigenetics regulator. However, its roles in liver carcinogenesis remain to be investigated. METHODS: Gene expressions were determined by RNA-Seq and qRT-PCR. G9a knockdown and knockout cell lines were established by lentiviral-based shRNA and CRISPR/Cas9 gene editing system. Tumor promoting functions of G9a was studied by both in HCC cell lines and nude mice model...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527816/adar1-is-targeted-by-mir-143-to-regulate-il-1%C3%AE-induced-endothelial-activation-through-the-nf%C3%AE%C2%BAb-pathway
#5
Yuanzhuo Chen, Hu Peng, Shuqin Zhou, Yugang Zhuang
Excessive endothelial activation by inflammatory mediators is a critical contributing factor of sepsis pathophysiology. ADAR1 (adenosine deaminase acting on RNA), an enzyme that binds and edits double-stranded RNAs, exhibits immune regulatory properties. Whether ADAR1 is involved in the pathophysiology of sepsis is unclear. In the present study, we used human umbilical endothelial cells (HUVECs) as an in vitro model system to investigate the roles of ADAR1 in interleukin (IL)-1β-induced endothelial activation...
May 17, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28525578/cell-type-specific-genome-editing-with-a-microrna-responsive-crispr-cas9-switch
#6
Moe Hirosawa, Yoshihiko Fujita, Callum J C Parr, Karin Hayashi, Shunnichi Kashida, Akitsu Hotta, Knut Woltjen, Hirohide Saito
The CRISPR-Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR-Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28524166/homology-mediated-end-joining-based-targeted-integration-using-crispr-cas9
#7
Xuan Yao, Xing Wang, Xinde Hu, Zhen Liu, Junlai Liu, Haibo Zhou, Xiaowen Shen, Yu Wei, Zijian Huang, Wenqin Ying, Yan Wang, Yan-Hong Nie, Chen-Chen Zhang, Sanlan Li, Leping Cheng, Qifang Wang, Yan Wu, Pengyu Huang, Qiang Sun, Linyu Shi, Hui Yang
Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome...
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28523919/editing-plants-for-virus-resistance-using-crispr-cas
#8
J C Green, J S Hu
This minireview summarizes recent advancements using the clustered regularly interspaced palindromic repeats-associated nuclease systems (CRISPR-Cas) derived from prokaryotes to breed plants resistant to DNA and RNA viruses. The CRISPR-Cas system represents a powerful tool able to edit and insert novel traits into plants precisely at chosen loci offering enormous advantages to classical breeding. Approaches to engineering plant virus resistance in both transgenic and non-transgenic plants are discussed. Iterations of the CRISPR-Cas system, FnCas9 and C2c2 capable of editing RNA in eukaryotic cells offer a particular advantage for providing resistance to RNA viruses which represent the great majority of known plant viruses...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28523551/epigenetic-mechanisms-of-gene-regulation-in-amyotrophic-lateral-sclerosis
#9
Alba Jimenez-Pacheco, Jaime M Franco, Soledad Lopez, Juan Miguel Gomez-Zumaquero, Maria Magdalena Leal-Lasarte, Diana E Caballero-Hernandez, Marta Cejudo-Guillén, David Pozo
Despite being clinically described 150 years ago, the mechanisms underlying amyotrophic lateral sclerosis (ALS) pathogenesis have not yet been fully understood. Studies in both animal models of ALS and human patients reveal a plethora of alterations such as increased glutamate-mediated excitotoxicity, redox stress, increased apoptosis, defective axonal transport, protein-misfolding events, mitochondrial impairment and sustained unregulated immune responses. Regardless of being sporadic or familiar ALS, the final outcome at the cellular level is the death of upper and lower motor neurons, and once diagnosed, ALS is typically lethal within the next 5 years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522803/precise-genome-wide-base-editing-by-the-crispr-nickase-system-in-yeast
#10
Atsushi Satomura, Ryosuke Nishioka, Hitoshi Mori, Kosuke Sato, Kouichi Kuroda, Mitsuyoshi Ueda
The CRISPR/Cas9 system has been applied to efficient genome editing in many eukaryotic cells. However, the bases that can be edited by this system have been limited to those within the protospacer adjacent motif (PAM) and guide RNA-targeting sequences. In this study, we developed a genome-wide base editing technology, "CRISPR Nickase system" that utilizes a single Cas9 nickase. This system was free from the limitation of editable bases that was observed in the CRISPR/Cas9 system, and was able to precisely edit bases up to 53 bp from the nicking site...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522548/a-multi-purpose-toolkit-to-enable-advanced-genome-engineering-in-plants
#11
Tomas Cermak, Shaun J Curtin, Javier Gil-Humanes, Radim Čegan, Thomas J Y Kono, Eva Konečná, Joseph J Belanto, Colby G Starker, Jade W Mathre, Rebecca L Greenstein, Daniel F Voytas
We report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on TALENs and the CRISPR/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination...
May 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28522157/antiviral-goes-viral-harnessing-crispr-cas9-to-combat-viruses-in-humans
#12
REVIEW
Jasper Adriaan Soppe, Robert Jan Lebbink
The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy...
May 15, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28521784/functional-regression-method-for-whole-genome-eqtl-epistasis-analysis-with-sequencing-data
#13
Kelin Xu, Li Jin, Momiao Xiong
BACKGROUND: Epistasis plays an essential rule in understanding the regulation mechanisms and is an essential component of the genetic architecture of the gene expressions. However, interaction analysis of gene expressions remains fundamentally unexplored due to great computational challenges and data availability. Due to variation in splicing, transcription start sites, polyadenylation sites, post-transcriptional RNA editing across the entire gene, and transcription rates of the cells, RNA-seq measurements generate large expression variability and collectively create the observed position level read count curves...
May 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28521126/structural-and-functional-architecture-of-ampa-type-glutamate-receptors-and-their-auxiliary-proteins
#14
REVIEW
Ingo H Greger, Jake F Watson, Stuart G Cull-Candy
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction elements at synapses and are critical for the expression of plasticity. The kinetic and conductance properties of AMPARs are laid down during their biogenesis and are regulated by post-transcriptional RNA editing, splice variation, post-translational modification, and subunit composition...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#15
Ivan Krivega, Ann Dean
Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520766/transcriptomic-analysis-of-salt-stress-responsive-genes-in-rhazya-stricta
#16
Nahid H Hajrah, Abdullah Y Obaid, Ahmed Atef, Ahmed M Ramadan, Dhivya Arasappan, Charllotte A Nelson, Sherif Edris, Mohammed Z Mutwakil, Alawia Alhebshi, Nour O Gadalla, Rania M Makki, Madgy A Al-Kordy, Fotouh M El-Domyati, Jamal S M Sabir, Mohammad A Khiyami, Neil Hall, Ahmed Bahieldin, Robert K Jansen
Rhazya stricta is an evergreen shrub that is widely distributed across Western and South Asia, and like many other members of the Apocynaceae produces monoterpene indole alkaloids that have anti-cancer properties. This species is adapted to very harsh desert conditions making it an excellent system for studying tolerance to high temperatures and salinity. RNA-Seq analysis was performed on R. stricta exposed to severe salt stress (500 mM NaCl) across four time intervals (0, 2, 12 and 24 h) to examine mechanisms of salt tolerance...
2017: PloS One
https://www.readbyqxmd.com/read/28516429/cardinal-epigenetic-role-of-non-coding-regulatory-rnas-in-circadian-rhythm
#17
REVIEW
Utpal Bhadra, Pradipta Patra, Manika Pal-Bhadra
Circadian rhythm which governs basic physiological activities like sleeping, feeding and energy consumption is regulated by light-controlled central clock genes in the pacemaker neuron. The timekeeping machinery with unique transcriptional and post-transcriptional feedback loops is controlled by different small regulatory RNAs in the brain. Roles of the multiple neuronal genes, especially post-transcriptional regulation, splicing, polyadenylation, mature mRNA editing, and stability of translation products, are controlled by epigenetic activities orchestrated via small RNAs...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28506212/guideseq-a-bioconductor-package-to-analyze-guide-seq-datasets-for-crispr-cas-nucleases
#18
Lihua Julie Zhu, Michael Lawrence, Ankit Gupta, Hervé Pagès, Alper Kucukural, Manuel Garber, Scot A Wolfe
BACKGROUND: Genome editing technologies developed around the CRISPR-Cas9 nuclease system have facilitated the investigation of a broad range of biological questions. These nucleases also hold tremendous promise for treating a variety of genetic disorders. In the context of their therapeutic application, it is important to identify the spectrum of genomic sequences that are cleaved by a candidate nuclease when programmed with a particular guide RNA, as well as the cleavage efficiency of these sites...
May 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28502110/a-novel-frameshift-mutation-of-the-adar1-gene-in-a-chinese-patient-with-dyschromatosis-symmetrica-hereditaria-and-the-dermoscopic-features
#19
Cheng Chi, Yixin Luo, Jie Liu
Dyschromatosis symmetrica hereditaria (DSH), which characterized by hyper- or hypopigmented macules on the dorsal aspect of distal extremities and freckle-like macules on the face, is a rare pigmented genodermatosis that usually restricted to the skin. Generally, DSH is considered autosomal dominant, and adenosine deaminase acting on the RNA-1 (ADAR1) gene is one of the responsible genes [1]. ADAR catalyses adenosine-to-inosine (A-to-I) editing of dsRNA substrates, which plays an important role in posttranscriptional regulatory processes...
May 14, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28502081/simultaneous-modification-of-three-homoeologs-of-taedr1-by-genome-editing-enhances-powdery-mildew-resistance-in-wheat
#20
Yunwei Zhang, Yang Bai, Guangheng Wu, Shenghao Zou, Yongfang Chen, Caixia Gao, Dingzhong Tang
Wheat (Triticum aestivum L.) incurs significant yield losses from powdery mildew, a major fungal disease caused by Blumeria graminis f. sp. tritici, (Bgt). ENHANCED DISEASE RESISTANCE1 (EDR1) plays a negative role in the defense response against powdery mildew in Arabidopsis thaliana; however, the edr1 mutant does not show constitutively activated defense responses. This makes EDR1 an ideal target for approaches using new genome-editing tools to improve powdery mildew resistance. We cloned TaEDR1 from hexaploid wheat and found high similarity among the three homoeologs of EDR1...
May 14, 2017: Plant Journal: for Cell and Molecular Biology
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