A unique spatial arrangement of the snRNPs within the native spliceosome emerges from in silico studies

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Highlights? We present a computational procedure for fast matching of thousands of conformers ? We obtained a unique model localizing the snRNPs within the native spliceosome ? The 5 snRNPs are accommodated mostly within the large subunit of the spliceosome ? The large spliceosomal cavity emerges as the site of mRNA binding and splicing     

Sequestration of DROSHA and DGCR8 by Expanded CGG RNA Repeats Alters MicroRNA Processing in Fragile X-Associated Tremor/Ataxia Syndrome

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Highlights? DGCR8 binds to CGG RNA repeats, cause of the neurodegenerative FXTAS disease ? DGCR8 and its partner, DROSHA, are sequestered within CGG RNA aggregates ? DGCR8 rescues the neuronal cell death induced by expanded CGG RNA repeats ? MicroRNA processing is impaired in patients with FXTAS     

Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits

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Highlights? Diminished PTB expression is sufficient to trans-differentiate fibroblasts to neurons ? PTB plays a key role in a regulatory loop to suppress neuronal-specific genes ? PTB regulates gene expression at both the splicing and RNA stability levels ? PTB modulates microRNA targeting by competition or switching RNA structure     

The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways

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Highlights? PGAM5 is a mitochondrial phosphatase that functions in programmed necrosis (necroptosis) ? Both splicing variants of PGAM5, PGAM5L and PGAM5S, are required for necroptosis ? PGAM5 dephosphorylates and activates mitochondrial fission protein Drp1 ? PGAM5 is required for necrosis induced by TNF-α, ROS, and calcium overload     

Replication Fork Stability Is Essential for the Maintenance of Centromere Integrity in the Absence of Heterochromatin

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Highlights? Fork protection complex protects centromeric repeats when heterochromatin is lost ? Mutants lacking heterochromatin and fork protection exhibit increased recombination ? Prolonged condensation in mutants lacking both heterochromatin and fork protection     

The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. elegans

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Highlights? UNC-45 self-assembles a docking platform for multiple chaperone and client proteins ? Hsp70/90 and myosin bind to specific sites on the TPR and UCS domains of UNC-45 ? The UNC-45 multimer offers the proper spacing to couple myosin folding and assembly ? In vivo, UNC-45 chains support the formation of fully functional sarcomeric repeats     

In Vivo Epigenomic Profiling of Germ Cells Reveals Germ Cell Molecular Signatures

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Highlights? Modified small-scale ChIP-seq method applicable to small number of cells ? Genome-wide maps of H3K4me3, H3K27me3, H3K27ac, and H2BK20ac of germ cells in vivo ? Identification of active and inactive regulatory elements in germ cells in vivo ? Germ cell H3K27me3 regions are enriched for retrotransposon repeats     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

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Highlights? Missing domains in PFV intasome revealed by SAXS/SANS ? PFV IN undergoes dramatic changes in conformation and oligomerization upon binding DNA ? Strand transfer inhibitors do not alter quaternary structure of PFV intasome     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11     

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

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Highlights? Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ? Solution biophysical analysis of ATP-dependent RIG-I conformational change ? The structural basis for ATP-stimulated RIG-I activation