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| Open AccessmiRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1
Several microRNAs have been implicated in the differentiation of immune cells. Here the authors analyse the global microRNA expression profiles of mouse haematopoietic stem cells and different stages of dendritic cell development and identify Notch1 as a target of miR-30b in regulatory dendritic cells.
- Xiaoping Su
- , Cheng Qian
- & Xuetao Cao
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Article
| Open AccessRibosome profiling reveals features of normal and disease-associated mitochondrial translation
Mitochondrial ribosomes are uniquely affected by mutations in the mitochondrial genome. By mapping the position of ribosomes on transcripts, the authors here reveal functional differences between mitochondrial and cytosolic ribosomes, and show that mutations in mitochondrial tRNAs induce ribosome stalling.
- Koos Rooijers
- , Fabricio Loayza-Puch
- & Reuven Agami
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| Open AccessMicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice
The micro-RNA miR-33 is encoded by an intron of the gene encoding sterol regulatory-binding protein 2 (SREBP-2) and controls cholesterol homoeostasis. Here, Horie et al.identify SREBP-1 as a target of miR-33 and show that deletion of miR-33 promotes diet-induced obesity and liver steatosis in mice.
- Takahiro Horie
- , Tomohiro Nishino
- & Koh Ono
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Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer
Whether microRNA processing mediated by Dicer is regulated in a cell-cycle-dependent manner is unknown. Here, Chen et al.show that Cyclin D1, which is important in the control of the cell cycle, regulates the expression of Dicer, and that Cyclin D1 and Dicer expression levels correlate in breast cancer.
- Zuoren Yu
- , Liping Wang
- & Richard G. Pestell
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Stepwise histone modifications are mediated by multiple enzymes that rapidly associate with nascent DNA during replication
Chromatin marks have to be re-established after DNA replication. Here Petruk et al. show that many histone-modifying enzymes are found in close proximity to newly replicated DNA in cells of Drosophilaembryos before the corresponding histone marks are re-established.
- Svetlana Petruk
- , Kathryn L. Black
- & Alexander Mazo
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A quantitative telomeric chromatin isolation protocol identifies different telomeric states
The protein composition of telomeres changes during development, aging, tumourigenesis and in telomere syndromes. Here, the authors develop a quantitative telomeric chromatin isolation protocol (QTIP) to analyse and quantitatively compare telomeric chromatin of different cell populations.
- Larissa Grolimund
- , Eric Aeby
- & Joachim Lingner
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miR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos
The microRNAs miR-1 and miR-206 have identical seed sequences and have been reported to regulate angiogenesis in zebrafish by repressing VegfAa expression. Here, Lin et al.describe opposing roles of the two microRNAs in regulating VegfAa expression and therefore angiogenesis in zebrafish.
- Cheng-Yung Lin
- , Hung-Chieh Lee
- & Huai-Jen Tsai
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Article
| Open AccessAnalogue encoding of physicochemical properties of proteins in their cognate messenger RNAs
mRNA transport contributes to the proper localization of its cognate proteins. Here the authors report a correlation between the physicochemical properties of mRNAs and their cognate proteins, suggesting that these properties of mRNAs can predict the subcellular localization of their cognate proteins.
- Anton A. Polyansky
- , Mario Hlevnjak
- & Bojan Zagrovic
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MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination
Meiotic recombination enables reciprocal exchange of genetic material between paternal and maternal homologous chromosomes. Here Luo et al.show that MEIOB, a novel meiosis-specific factor identified in a proteomics screen, forms complexes with RPA2 and SPATA22, and is required for meiotic recombination.
- Mengcheng Luo
- , Fang Yang
- & P. Jeremy Wang
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VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
Toxin–antitoxin systems have been implicated in the pathogenicity of Mycobacterium tuberculosis. Here, the authors study the function of the M. tuberculosistoxin VapC20 and show that it can impair protein translation and inhibit bacterial growth by cleaving the Sarcin–Ricin loop of 23S rRNA
- Kristoffer S. Winther
- , Ditlev E. Brodersen
- & Kenn Gerdes
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Article
| Open AccessIdentification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif
AGO-CLIP permits the identification of miRNA target genes. Here, Hamilton et al. compile publicly available AGO-CLIP data and combine this information with miRNA analysis from The Cancer Genome Atlas, permitting the identification of an oncogenic miRNA superfamily that targets tumour suppressor genes.
- Mark P. Hamilton
- , Kimal Rajapakshe
- & Sean E. McGuire
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Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase
SAMHD1 is a dNTP hydrolase that has been shown to act as a restriction factor against retroviruses such as HIV, and also regulates the retrotransposition of LINE-1 elements. Here the authors reveal the structural basis for dGTP-dependent tetramerization and allosteric activation of the enzyme.
- Chunfeng Zhu
- , Wenying Gao
- & Xiao-Fang Yu
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RNA editing regulates transposon-mediated heterochromatic gene silencing
The Hoppel transposable element mediates heterochromatin formation in Drosophila. Here Savva et al. report that the RNA-editing enzyme, ADAR, edits a long double-stranded RNA generated by the Hoppeltransposon, thereby regulating heterochromatin formation and gene expression.
- Yiannis A. Savva
- , James E. C. Jepson
- & Robert A. Reenan
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Involvement of parental imprinting in the antisense regulation of onco-miR-372-373
The miR-372-3 cluster has a role in oncogenesis. In this study, by utilizing parthenogenetic induced pluripotent stem cells, that lack the paternal genome, Stelzer et al.report that these miR-372-3 are negatively regulated by a paternally imprinted antisense transcript and that loss of its expression promotes oncogenesis.
- Yonatan Stelzer
- , Ido Sagi
- & Nissim Benvenisty
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Structural determinants of HIV-1 Vif susceptibility and DNA binding in APOBEC3F
APOBEC3F is a DNA cytosine deaminase involved in restriction of HIV-1, but its activity can be suppressed by the viral protein Vif. Here, the authors provide insights into the interaction between these two proteins by determining the structure of the APOBEC3F Vif-binding domain.
- Karen K. Siu
- , Azmiri Sultana
- & Jeffrey E. Lee
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ARF triggers senescence in Brca2-deficient cells by altering the spectrum of p53 transcriptional targets
The tumour suppressor ARF regulates p53 levels; however, in contrast to p53, ARF has not been implicated in the response to DNA damage. In this study, Carlos et al.show that single-stranded DNA formed in BRCA2-null cells triggers a DNA damage response leading to the activation of ARF and senescence.
- Ana Rita Carlos
- , Jose Miguel Escandell
- & Madalena Tarsounas
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Semiconductor-based DNA sequencing of histone modification states
Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.
- Christine S. Cheng
- , Kunal Rai
- & Ido Amit
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Article
| Open AccessBase excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy
The chemotherapeutic drug 5-fluorouracil causes cell toxicity by inducing DNA lesions. Here, SenGupta et al. use C. elegansto show that components of the base excision repair and the mismatch repair pathways function together in the response to 5-fluorouracil, resulting in activation of the DNA damage checkpoint and induction of autophagy.
- Tanima SenGupta
- , Maria Lyngaas Torgersen
- & Hilde Nilsen
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| Open AccessHeterozygous mutations in PALB2 cause DNA replication and damage response defects
PALB2 is a BRCA1-/BRCA2-interacting protein and heterozygous mutations in PALB2 are associated with hereditary breast cancer predisposition. Here the authors show that human lymphoblastoid cells from heterozygous PALB2mutation carriers display abnormal DNA replication dynamics and DNA damage response.
- Jenni Nikkilä
- , Ann Christin Parplys
- & Robert Winqvist
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Cdkn1b overexpression in adult mice alters the balance between genome and tissue ageing
Reduced rates of cell proliferation are thought to contribute to age-related tissue dysfunction. Here Pruitt et al.induce expression of the cell cycle inhibitor Cdkn1b in adult mice and show that this recapitulates ageing-related defects in tissue maintenance.
- Steven C. Pruitt
- , Amy Freeland
- & Gillian K. Cady
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Article
| Open AccessHigh genome heterozygosity and endemic genetic recombination in the wheat stripe rust fungus
Stripe rust is one of the most destructive wheat diseases. Here, Zheng and colleagues report a draft genome sequence of wheat stripe rust fungus, generated using a fosmid-to-fosmid approach, and provide insight into its race evolution and pathogenesis.
- Wenming Zheng
- , Lili Huang
- & Zhensheng Kang
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Separation of a functional deubiquitylating module from the SAGA complex by the proteasome regulatory particle
The SAGA transcriptional coactivator is modulated by the 19S proteasome to increase the interaction of SAGA with transcription activators. Here, Limet al.show that the 19S proteasome mediates dissociation of a submodule of the SAGA complex in a non-proteolytic manner, which is implicated in mRNA export in yeast.
- Sungsu Lim
- , Jaechan Kwak
- & Daeyoup Lee
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Torque modulates nucleosome stability and facilitates H2A/H2B dimer loss
Histone H2A-H2B heterodimers are lost from nucleosomes during transcription by RNA polymerase II. Here Sheinin et al. investigate the behaviour of single nucleosomes subjected to DNA supercoiling and observe a loss of these heterodimers under positive supercoiling, which might have implications for histone turnover during transcription in vivo.
- Maxim Y. Sheinin
- , Ming Li
- & Michelle D. Wang
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Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes
Condensins participate in the packaging of chromatin during mitosis. Kim et al. discover that condensin I concentrates in centromeres, telomeres and the promoters of active genes in vertebrates, revealing that condensin distribution is remarkably conserved across phylogeny.
- Ji Hun Kim
- , Tao Zhang
- & Damien F. Hudson
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Metastasis-associated protein 1 is an integral component of the circadian molecular machinery
Mammalian circadian clocks modulate the daily cycles of many cellular processes. Here the authors find that metastasis-associated protein 1, which is upregulated in human cancers, is an intrinsic regulator of the mammalian molecular clock.
- Da-Qiang Li
- , Suresh B. Pakala
- & Rakesh Kumar
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Darwinian evolution in a translation-coupled RNA replication system within a cell-like compartment
Molecular evolution events are vital for the development of cellular complexity. Here the authors construct an evolvable artificial cell model, and observe that Darwinian evolution leads to more efficient RNA replication over time.
- Norikazu Ichihashi
- , Kimihito Usui
- & Tetsuya Yomo
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miRNAs confer phenotypic robustness to gene networks by suppressing biological noise
MicroRNAs are thought to confer robustness to biological processes, but clear experimental evidence is still needed. Here, Siciliano et al. construct a toggle-switch in mammalian cells to show that microRNAs buffer fluctuations in protein levels, thereby providing phenotypic robustness to gene regulatory networks.
- Velia Siciliano
- , Immacolata Garzilli
- & Diego di Bernardo
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Gene regulation and priming by topoisomerase IIα in embryonic stem cells
Topoisomerase 2α (Top2α) has essential roles during DNA replication, whereas its isoform Top2β is implicated in gene expression. Thakurela et al.show that Top2α is also required for stem-cell transcriptome regulation and primes developmental genes for activation by Top2β upon terminal differentiation.
- Sudhir Thakurela
- , Angela Garding
- & Vijay K. Tiwari
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Article
| Open AccessStructure of a helicase–helicase loader complex reveals insights into the mechanism of bacterial primosome assembly
During the initiation of bacterial DNA replication, loader proteins transfer the hexameric helicase ring onto replication origin DNA. Liu et al.report the crystal structure of a 570-kDa prepriming complex and suggest that the release of loader proteins is associated with the transition of the helicase ring to a spiral configuration.
- Bin Liu
- , William K. Eliason
- & Thomas A. Steitz
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MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation
MBNL and FOX splicing factors are known to have a role in the differentiation of muscle and the nervous system during development. In this study, the authors show that MBNL1 and RBFOX2 regulate alternative splicing of genes that are required specifically for late mesoderm differentiation.
- Julian P. Venables
- , Laure Lapasset
- & Jamal Tazi
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Article
| Open AccessHydrogenosomes in the diplomonad Spironucleus salmonicida
Hydrogenosomes and mitosomes are mitochondria-related organelles with distinct properties. Here the authors find that the mitochondria-related organelle of the salmon parasite Spironucleus salmonicidahas characteristics of both diplomonad mitosomes and of parabasalid hydrogenosomes, suggesting the presence of hydrogenosomes in the last common ancestor.
- Jon Jerlström-Hultqvist
- , Elin Einarsson
- & Staffan G. Svärd
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Tumour angiogenesis regulation by the miR-200 family
The microRNA-200 family members have a role in regulating tumour angiogenesis but the underlying mechanism is unclear. In this study, Pecot et al.demonstrate that miR-200 affects angiogenesis by altering endothelial and cancer cell cytokine secretion.
- Chad V. Pecot
- , Rajesha Rupaimoole
- & Anil K. Sood
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Article
| Open AccessRecG and UvsW catalyse robust DNA rewinding critical for stalled DNA replication fork rescue
The helicases UvsW and RecG have both unwinding and rewinding activities and are involved in the rescue of stalled DNA replication forks. Here Manosas et al. use single-molecule techniques to characterize the rewinding activities of the two helicases, concluding that rewinding is actively catalysed.
- Maria Manosas
- , Senthil K. Perumal
- & Vincent Croquette
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HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA
The nuclear protein HMGB1 is involved in muscle fibre formation. Here, Dormoy-Raclet et al. show that during muscle cell differentiation, the RNA-binding protein HuR promotes HMGB1mRNA translation by preventing its repression by miR-1192.
- Virginie Dormoy-Raclet
- , Anne Cammas
- & Imed-Eddine Gallouzi
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Article
| Open AccessHuman DNA helicase HELQ participates in DNA interstrand crosslink tolerance with ATR and RAD51 paralogs
Agents that cause DNA interstrand crosslinks are widely used to treat cancer. Takata et al.show that the DNA helicase HELQ associates with ATR and RAD51 paralogs, which are components of DNA repair pathways, and helps defend human cells against agents that induce DNA interstrand crosslinks.
- Kei-ichi Takata
- , Shelley Reh
- & Richard D. Wood
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Article
| Open AccessA versatile cis-acting inverter module for synthetic translational switches
Artificial genetic circuits have been designed to enable precise control of cellular behaviour and phenotypes. Saito and colleagues present a new RNA module that can invert the function of a translational OFF to an ON switch and demonstrate its utility in mammalian cells.
- Kei Endo
- , Karin Hayashi
- & Hirohide Saito
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An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms
Protein deacetylases of the sirtuin family have important roles in aging and metabolism. Using peptide microarrays displaying physiological lysine acetylation sites, the authors map the substrate preferences of all seven human sirtuin isoforms, revealing enzyme specificities and identifying new sirtuin substrates.
- David Rauh
- , Frank Fischer
- & Clemens Steegborn
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BRCA1 and CtIP suppress long-tract gene conversion between sister chromatids
Absence of Brca2 or Rad51 paralogues biases homologous recombination towards the error-prone outcome of long-tract gene conversion. Here, the authors report that BRCA1, together with the end resection protein CtIP, controls the balance between short- and long-tract gene conversion, thereby affecting the fidelity of homologous recombination.
- Gurushankar Chandramouly
- , Amy Kwok
- & Ralph Scully
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Article
| Open AccessWall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens
Horizontal gene transfer of mobile genetic elements contributes to bacterial evolution and emergence of new pathogens. Here the authors demonstrate that the highly diverse structure of wall teichoic acid polymers governs horizontal gene transfer among Gram-positive pathogens, even across long phylogenetic distances.
- Volker Winstel
- , Chunguang Liang
- & Guoqing Xia
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Article
| Open AccessATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy
The protein ATG5 is known to be involved in the formation of autophagosomes. Here, Maskey et al. identify a new role of ATG5 in response to drug-induced DNA damage whereby ATG5 translocates to the nucleus, leading to chromosome misalignment and mitotic catastrophe.
- Dipak Maskey
- , Shida Yousefi
- & Hans-Uwe Simon
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Mechanism for full-length RNA processing of Arabidopsis genes containing intragenic heterochromatin
Transposable elements found within transcribed regions of genes are often compacted into heterochromatin. Using Arabidopsisas a model, these authors show that the protein, IBM2, is required for correct processing of genes that contain intragenic heterochromatin.
- Hidetoshi Saze
- , Junko Kitayama
- & Tetsuji Kakutani
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Article
| Open AccessEndonuclease V cleaves at inosines in RNA
Bacterial endonuclease V enzymes are characterized as DNA repair proteins. Here the authors show that human endonuclease V is an inosine-specific ribonuclease, indicating a role for this enzyme in normal RNA metabolism rather than DNA repair.
- Erik Sebastian Vik
- , Meh Sameen Nawaz
- & Ingrun Alseth
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Article
| Open AccessHuman endonuclease V is a ribonuclease specific for inosine-containing RNA
In Escherichia coli, the highly conserved enzyme endonuclease V has a role in DNA repair. Here the authors show that human endonuclease V is an inosine 3' endoribonuclease and that Tudor Staphylococcal nuclease enhances this activity, suggesting a role for human endonuclease V in RNA metabolism.
- Yoko Morita
- , Toshihiro Shibutani
- & Isao Kuraoka
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PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine
Tet proteins control DNA demethylation, but how the DNA target regions are determined is unclear. Here the authors report that during adipocyte differentiation, PPARγ binds to the PPAR-response element and recruits Tet proteins, thereby inducing local DNA demethylation.
- Katsunori Fujiki
- , Akihiro Shinoda
- & Masayuki Murata
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Dissecting the role of H3K64me3 in mouse pericentromeric heterochromatin
H3K64 trimethylation on the nucleosome lateral surface marks pericentric heterochromatin. Here Lange et al.show that H3K64me3 enrichment ensures heterochromatin integrity and occurs in an H3K9me3-dependent, but an H4K20me3- and heterochromatin protein 1-independent manner.
- Ulrike C. Lange
- , Stéphanie Siebert
- & Robert Schneider
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Tertiary structural elements determine the extent and specificity of messenger RNA editing
A central, imperfect duplex RNA secondary structure is generally required for site-specific adenosine-to-inosine RNA editing by ADAR enzymes. Rieder et al. show in Drosophila that conserved and complex long-range RNA tertiary structures form in vivoand can also regulate specific RNA-editing events by ADAR enzymes.
- Leila E. Rieder
- , Cynthia J. Staber
- & Robert A. Reenan
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Genome-wide search for exonic variants affecting translational efficiency
Genetic effects on gene expression by variants at expression quantitative trait loci (eQTLs), can contribute to human genetic diseases. Here, Liet al. present a method to study eQTLs with effects on protein translation on a transcriptome-wide scale.
- Quan Li
- , Angeliki Makri
- & Hui-Qi Qu
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The RAG2 C-terminus and ATM protect genome integrity by controlling antigen receptor gene cleavage
Mice lacking the C-terminal non-core domain of RAG2 and ATM mutant mice develop thymic lymphomas harbouring recurrentTcra/d–Ightranslocations. Here the authors show that ATM and the non-core domain of RAG2 prevent bi-locus recombination by modulating higher-order chromatin structure.
- Julie Chaumeil
- , Mariann Micsinai
- & Jane A. Skok
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The effects of carbon dioxide and temperature on microRNA expression in Arabidopsis development
An increase in the concentration of atmospheric carbon dioxide and warmer temperatures can alter plant growth and development. Here the authors show that these conditions can also elicit significant changes in microRNAs expression, including some which might induce early flowering in Arabidopsis.
- Patrick May
- , Will Liao
- & Qiong A. Liu
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