Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity

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Highlights? EM structure of the CMR complex for viral RNA degradation has been determined ? The crRNA content of CMR has been analyzed by deep sequencing ? Target RNA cleavage by CMR is sequence dependent     

Functional Classification of Immune Regulatory Proteins

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Highlights? An intermediate sequence based clustering algorithm, Brotherhood, is introduced ? The Brotherhood method is used to assign functional families within the human IgSF ? Newly annotated nectin-like family member, CRTAM, structure is solved ? Homophilic transinteraction is observed for CRTAM     

Essential features and rational design of CRISPR RNAs that function with the Cas RAMP module complex to cleave RNAs

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Highlights? CRISPR RNA function requires a conserved CRISPR sequence tag ? CRISPR RNAs can be engineered to direct cleavage of novel target RNAs ? The Cmr complex cleaves complementary RNAs in vivo     

The Glove-like Structure of the Conserved Membrane Protein TatC Provides Insight into Signal Sequence Recognition in Twin-Arginine Translocation

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Highlights? Crystal structures of TatC from the thermophile Aquifex aeolicus are presented ? The architecture of TatC generates a glove-shaped pocket buried in the bilayer ? Molecular dynamics reveal destabilization of the membrane around the pocket ? Correlation to biochemical results suggest the signal sequence binds in this pocket     

The SH2 Domain Interaction Landscape

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Highlights? The recognition specificity of 70 SH2 domains is probed ? Recognition specificity diverges faster than sequence ? PepspotDB is a database of protein interactions mediated by SH2 domains     

The Mitochondrial RNA-Binding Protein GRSF1 Localizes to RNA Granules and Is Required for Posttranscriptional Mitochondrial Gene Expression

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Highlights? GRSF1 (G-rich sequence binding factor 1) is a mitochondrial RNA-binding protein ? GRSF1 localizes to granules containing newly synthesized RNA in close proximity to mitochondrial nucleoids ? GRSF1 specifically binds one mRNA and two long noncoding RNAs transcribed from contiguous genes on the light strand of mtDNA ? Loss of GRSF1 leads to misloading of RNAs onto the mitochondrial ribosome and a specific translation defect     

Rare Codons Regulate KRas Oncogenesis

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Highlights? Mammalian KRAS is enriched in rare codons that limit its expression ? Changing rare to common codons increases ectopic and endogenous KRAS expression ? KRAS oncogenicity is limited by rare codons ? Other gene pairs exhibit high sequence identity but opposing codon bias     

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     

DNA Minor Groove Sensing and Widening by the CCAAT-Binding Complex

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Highlights? CBC binds to the minor groove of the DNA and bends it in a nucleosome-like manner ? Interactions of subunit HapB with DNA explain the sequence specificity of the CBC ? Anchor A of HapB tethers the CBC to the CCAAT box by minor groove widening ? Interactions of the CBC with the histones H3/H4 of the nucleosome are modeled     

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     

The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b

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Highlights? The CDK9 C-terminal tail is important for the catalytic mechanism ? CDK9 phosphorylates the CTD in a nonprocessive manner ? The CDK9 tail folds over the ATP binding site during the catalytic cycle     

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     

Structural and functional analysis of HtrA1 and its subdomains

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Highlights? IGFBP-like domain structure suggests that it is incompetent for IGF binding ? Kazal-like domain structure shows distorted “P1” loop incompetent for inhibition ? Protease domain shows catalytic readiness in apo form ? SAXS envelope for full-length HtrA1     

Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine

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Highlights? The structure of ketamine-bound GLIC reveals an anesthetic binding site ? The study provides compelling evidence for allosteric inhibition by anesthetics ? Ketamine inhibition on GLIC is similar to competitive antagonist action on nAChRs ? Ketamine directly acts on pLGICs in addition to NMDA receptors     

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis

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Highlights? Discovery that Rspo3 binds syndecan 4 ? Rspo3/Sdc4 induce Wnt/PCP signaling via clathrin-mediated endocytosis ? Rspo3/PCP signaling is essential for gastrulation and cartilage morphogenesis     

The Cotranslational Function of Ribosome-Associated Hsp70 in Eukaryotic Protein Homeostasis

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Highlights? Yeast Hsp70 SSB binds cotranslationally to a defined set of nascent polypeptides ? SSB shows specificity for substrates highly challenged in cotranslational folding ? The heterodimeric cochaperone RAC modulates cotranslational SSB specificity ? Loss of SSB function leads to widespread misfolding and aggregation     

Functional identification of optimized RNAi triggers using a massively parallel sensor assay

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Highlights? The Sensor assay reliably identifies potent single-copy shRNAs ? Potent shRNAs are rare and generally not predicted by existing algorithms ? Analyses of ～20,000 shRNAs reveal insights into shRNA biogenesis and function ? Sensor-based rules provide a criteria framework for rational shRNA design     

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