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CpxR Activates MexAB-OprM Efflux Pump Expression and Enhances Antibiotic Resistance in Both Laboratory and Clinical nalB-Type Isolates of Pseudomonas aeruginosa

Oct 14，2016

Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified upstream of the mexA promoter in all genome-sequenced P. aeruginosa strains. CpxR is required to enhance mexAB-oprM expression and drug resistance, in the absence of repressor MexR, in P. aeruginosa strains PA14. As defective mexR is a genetic trait associated with the clinical emergence of nalB-type multidrug resistance in P. aeruginosa during antibiotic treatment, we investigated the involvement of CpxR in regulating multidrug resistance among resistant isolates generated in the laboratory via antibiotic treatment and collected in clinical settings. CpxR is required to activate expression of mexAB-oprM and enhances drug resistance, in the absence or presence of MexR, in ofloxacin-cefsulodin-resistant isolates generated in the laboratory. Furthermore, CpxR was also important in the mexR-defective clinical isolates. The newly identified regulatory linkage between CpxR and the MexAB-OprM efflux pump highlights the presence of a complex regulatory network modulating multidrug resistance in P. aeruginosa.

3Disease Browser: A Web server for integrating 3D genome and disease-associated chromosome rearrangement data

Oct 14，2016

Chromosomal rearrangement (CR) events have been implicated in many tumor and non-tumor human diseases. CR events lead to their associated diseases by disrupting gene and protein structures. Also, they can lead to diseases through changes in chromosomal 3D structure and gene expression. In this study, we search for CR-associated diseases potentially caused by chromosomal 3D structure alteration by integrating Hi-C and ChIP-seq data. Our algorithm rediscovers experimentally verified disease-associated CRs (polydactyly diseases) that alter gene expression by disrupting chromosome 3D structure. Interestingly, we find that intellectual disability may be a candidate disease caused by 3D chromosome structure alteration. We also develop a Web server (3Disease Browser, http://3dgb.cbi.pku.edu.cn/disease/) for integrating and visualizing disease-associated CR events and chromosomal 3D structure.

Ubiquitin Ligases RGLG1 and RGLG5 Regulate Abscisic Acid Signaling by Controlling the Turnover of Phosphatase PP2CA

Oct 11，2016

Abscisic acid (ABA) is an essential hormone for plant development and stress responses.ABA signaling is suppressed by clade A PP2C phosphatases, which function as key repressors of this pathway through inhibiting ABA-activated SnRK2s (SNF1-related protein kinases). Upon ABA perception, the PYR/PYL/RCAR ABA receptors bind to PP2Cs with high affinity and biochemically inhibit their activity. While this mechanism has been extensively studied, how PP2Cs are regulated at the protein level is only starting to be explored. Arabidopsis thaliana RING DOMAIN LIGASE5 (RGLG5) belongs to a five-member E3 ubiquitin ligase family whose target proteins remain unknown. We report that RGLG5, together with RGLG1, releases the PP2C blockade of ABA signaling by mediating PP2CA protein degradation. ABA promotes the interaction of PP2CA with both E3 ligases, which mediate ubiquitination of PP2CA and are required for ABA-dependent PP2CA turnover. Downregulation of RGLG1 and RGLG5 stabilizes endogenous PP2CA and diminishes ABA-mediated responses. Moreover, the reduced response to ABA in germination assays is suppressed in the rglg1 amiR (artificial microRNA)-rglg5 pp2ca-1 triple mutant, supporting a functional link among these loci. Overall, our data indicate that RGLG1 and RGLG5 are important modulators of ABA signaling, and they unveil a mechanism for activation of the ABA pathway by controlling PP2C half-life.

Arabidopsis small nucleolar RNA monitors the efficient pre-rRNA processing during ribosome biogenesis

Oct 10，2016

Box C (RUGAUGA)/D (CUGA) and H (ANANNA)/ACA small nucleolar RNAs (snoRNAs) are important for the modification and processing of rRNA during ribosome biogenesis in eukaryotes. However, the molecular role of snoRNAs throughout the multiple steps of pre-rRNA processing remains poorly understood. This study shows that an uncharacterized C/D box snoRNA, HIDDEN TREASURE 2 (HID2), functions as a prominent player in the monitoring of efficient pre-rRNA processing, which, in turn, is essential for accurate ribosome assembly in Arabidopsis. Our data explore a link between a spatially regulated snoRNA and the complexity and the precise control of ribosome biogenesis. Further, the conservation of HID2’s signature motif and function highlights its importance in multicellular organisms. hid2 appears to be a representative snoRNA mutant exhibiting pleiotropic developmental defects in plants.

Dynamics of Escherichia coli’s passive response to a sudden decrease in external osmolarity

Sep 20，2016

Mechanosensation is central to life. Bacteria, like the majority of walled cells, live and grow under significant osmotic pressure. By relying on mechanosensitive regulation, bacteria can adapt to dramatic changes in osmotic pressure. Studying such mechanical sensing and control is critical for understanding bacterial survival in a complex host and natural environment. Here, we investigate the fundamental design principles of Escherichia coli’s passive mechanosensitive response to osmotic downshocks by implementing single-cell high-resolution imaging. We explain the observed cell volume changes by modeling flux of water and solutes across the cell membrane. A better characterization of bacterial mechanosensitive response can help us map their reaction to environmental threats.

Rice Dwarf Virus P2 Protein Hijacks Auxin Signaling by Directly Targeting the Rice OsIAA10 Protein, Enhancing Viral Infection and Disease Development

Sep 12，2016

Auxin regulates plant growth and development through auxin signaling, which begins with the interaction of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB) protein and an auxin/indole-3-acetic acid (Aux/IAA) protein co-receptor. Auxin binding to the co-receptor complex triggers ubiquitination and 26S proteasome degradation of Aux/IAA proteins, leading to a downstream signaling cascade that induces the expression of auxin-responsive genes. Auxin signaling is manipulated by plant pathogens to maximize their own multiplication, but the underlying mechanisms are poorly understood. Here we report that the P2 capsid protein encoded by Rice dwarf virus (RDV) sabotages auxin signaling by interacting with the rice Aux/IAA protein, OsIAA10, thereby shielding it from degradation and causing infected plants to display typical RDV symptoms including dwarfism, excessive tillering and stunted crown roots. Importantly, these symptoms are phenocopied by transgenic rice plants overexpressing OsIAA10 or its degradation-resistant mutant. Conversely, down-regulating OsIAA10 expression in rice led to milder RDV infection. Together these findings reveal a novel mechanism by which RDV reprograms auxin signaling, leading to enhanced viral infection.

The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth

Aug 29，2016

Dysfunctions in ribosome biogenesis cause developmental defects and increased cancer susceptibility; however, the connection between ribosome assembly and tumorigenesis remains unestablished. Here we show that hCINAP (also named AK6) is required for human 18S rRNA processing and 40S subunit assembly. Homozygous CINAP−/− mice show embryonic lethality. The heterozygotes are viable and show defects in 18S rRNA processing, whereas no delayed cell growth is observed. However, during rapid growth, CINAP haploinsufficiency impairs protein synthesis. Consistently, hCINAP depletion in fast-growing cancer cells inhibits ribosome assembly and abolishes tumorigenesis. These data demonstrate that hCINAP reduction is a specific rate-limiting controller during rapid growth. Notably, hCINAP is highly expressed in cancers and correlated with a worse prognosis. Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. Our results connect the role of hCINAP in ribosome assembly with tumorigenesis. Modulation of hCINAP expression may be a promising target for cancer therapy.

Crystal structure of PXY-TDIF complex reveals a conserved recognition mechanism among CLE peptide-receptor pairs

Aug 26，2016

Keywords: CLE peptides; receptor kinases; crystal structure; TDIF; PXY

SERK Family Receptor-Like Kinases Function as a Co-receptor with PXY for Plant Vascular Development

Aug 26，2016

SERK family receptor like kinases function as a co-receptor with PXY and are essential for plant vascular development. Structural analysis of PXY-TDIF-SERK2 complex reveals several conserved interacting motifs and suggests a conserved receptor activation mechanism among CLE and other small peptides.

Maternal ENODLs Are Required for Pollen Tube Reception in Arabidopsis

Aug 21，2016

•ENODL11–15 are GPI-anchored proteins, each with a plastocyanin-like domain •ENODL11–15 are predominantly expressed in the ovules and the funiculus •Loss of function or overexpression of ENODLs compromises pollen tube reception •ENODL14 has physical interaction with the extracellular domain of FERONIA

The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development

Aug 19，2016

Wingless (Wg)/Wnt signaling is conserved in all metazoan animals and plays critical roles in development. The Wg/Wnt morphogen reception is essential for signal activation, whose activity is mediated through the receptor complex and a scaffold protein Dishevelled (Dsh). We report here that the exon junction complex (EJC) activity is indispensable for Wg signaling by maintaining an appropriate level of Dsh protein for Wg ligand reception in Drosophila. Transcriptome analyses in Drosophila wing imaginal discs indicate that the EJC controls the splicing of the cell polarity gene discs large 1 (dlg1), whose coding prote¬in directly interacts with Dsh. Genetic and biochemical experiments demonstrate that Dlg1 protein acts independently from its role in cell polarity to protect Dsh protein from lysosomal degradation. More importantly, human orthologous Dlg protein is sufficient to promote Dvl protein stabilization and Wnt signaling activity, thus revealing a conserved regulatory mechanism of Wg/Wnt signaling by Dlg and EJC.

RNF123 has an E3 ligase‐independent function in RIG‐I‐like receptor‐mediated antiviral signaling

Aug 04，2016

The human RING finger family protein RNF123 inhibits RNA virus‐induced IFN‐β production independent of its E3 ubiquitin ligase activity by interacting with the CARD domains of RIG‐I/MDA5, thereby competing with the RIG‐I/MDA5 signaling adaptor VISA.

　