Cap-assisted internal initiation of translation of histone H4

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Highlights? Two structural elements of histone H4 mRNA drive translation initiation ? Ribosome is tethered by an eIF4E-binding site located in the coding region ? A RNA three-way helix junction element positions ribosome on the start codon ? The m⁷G cap-binding pocket formed by the mRNA controls histone translation     

CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration

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Highlights? Cullin 4A promotes the autoubiquitylation of Cdt2, a substrate adaptor of CRL4^Cdt2 ? CRL1^FBXO11 also ubiquitylates and promotes the degradation of Cdt2 ? FBXO11 degrades Cdt2 to stabilize Set8 and regulate the response to TGF-β ? FBXO11 is similarly required to stabilize Set8 and promote cell migration     

Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development

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Highlights? Wnt2 is required for atrial and inflow tract morphogenesis ? Wnt2 regulates expansion of secondary heart field progenitors ? Defects in Wnt2^?/? mutants can be rescued using Wnt signaling agonists ? Wnt2 cooperates with Gata6 to regulate cardiac inflow tract development     

STIM1 Juxtaposes ER to Phagosomes,Generating Ca2+ Hotspots that Boost Phagocytosis

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Highlights? STIM1 drives store-operated recruitment of ER cisternae to phagosomes ? STIM1 is required for Ca²⁺-dependent, high-efficiency phagocytosis ? STIM1 gates phagosomal Ca²⁺ channels, generating periphagosomal Ca²⁺ microdomains     

Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair

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Highlights? c-kit⁺ cell therapy stimulates endogenous cardiomyocyte progenitors ? Nkx2.5- and Gata4-expressing progenitors increase in the infarct border zone ? c-kit⁺ cell therapy leads to improved cardiac function ? No evidence for cardiomyocyte transdifferentiation by bone marrow progenitors     

ADF/cofilin regulates secretory cargo sorting at the TGN via the Ca2+ ATPase SPCA1

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Highlights? ADF/cofilin localizes to the TGN and binds SPCA1 in an actin-dependent manner ? Dynamic actin regulates the activity of the Ca²⁺ pump SPCA1 ? ADF/cofilin facilitates secretory cargo sorting in a Ca²⁺-dependent manner     

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     

Development and Regeneration of Sox2+ Endoderm Progenitors Are Regulated by a HDAC1/2-Bmp4/Rb1 Regulatory Pathway

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Highlights? Hdac1/2 regulate development of Sox2+ endoderm progenitors ? Bmp4, Rb1, p21, and p16 are direct targets of Hdac1/2 in lung endoderm ? Increased Bmp4 suppresses Sox2 expression in lung endoderm ? Hdac1/2 are required for lung secretory epithelial regeneration     

Na+ Regulation in the Malaria Parasite Plasmodium falciparum Involves the Cation ATPase PfATP4 and Is a Target of the Spiroindolone Antimalarials

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Highlights? The intraerythrocytic malaria parasite extrudes Na⁺ via a Na⁺-ATPase ? Parasite Na⁺ homeostasis is disrupted by the antimalarial spiroindolones ? Mutations in PfATP4 confer resistance to Na⁺ disruption by the spiroindolones ? PfATP4 is postulated to be a Na⁺ efflux ATPase and a target of the spiroindolones     

Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression

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Highlights? An unstable MCM2-7 complex results in a loss of dormant origins in Mcm4^Chaos3 cells ? A loss of dormant origins impairs stalled fork recovery in unchallenged S phase ? A loss of dormant origins increases replication intermediates in prophase ? Replication intermediates in M phase are a likely cause of chromosome instability     

A master switch couples Mg²⁺-assisted catalysis to domain motion in B. stearothermophilus tryptophanyl-tRNA Synthetase

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Highlights? Combinatorial mutagenesis at four remote sites shifts reaction coordinate stabilities ? Cooperative action of all four sites accounts for the entire catalytic role of Mg2⁺ ? Catalysis of ATP utilization by Mg2⁺ occurs if, and only if, the conformation changes ? This type of allosteric effect may explain vectorial coupling in transducing NTPases     

Structure of Phosphorylated SF1 Bound to U2AF65 in an Essential Splicing Factor Complex

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Highlights? Splicing factor SF1 phosphorylation on a conserved SPSP motif is required in vivo ? SPSP phosphorylation (P) induces local folding within an SF1/U2AF⁶⁵ interface ? Phosphorylation promotes an acutely bent (P)SF1/U2AF⁶⁵/RNA conformation     

Cohesin-Dependent Association of Scc2/4 with the Centromere Initiates Pericentromeric Cohesion Establishment

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Highlights? Cohesin is required for the association of its loader, Scc2/4, with centromeres ? The Ctf19 kinetochore subcomplex targets the loader to centromeres ? Centromere-loaded cohesin ensures pericentromeric cohesion establishment ? Cohesin ring formation triggers cohesin loading via Scc2/4     

The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication

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Highlights? The Plk4 cryptic polo box is a structurally unique, tandem polo box array: PB1-PB2 ? Full length Plk4 comprises three polo box domains, a unique polo kinase architecture ? The Plk4 PB1-PB2 cassette is required for Asterless binding and centriole targeting ? The Plk4 PB1-PB2 homodimer potentiates Plk4 degradation     

Replacement of Oct4 by Tet1 during iPSC Induction Reveals an Important Role of DNA Methylation and Hydroxymethylation in Reprogramming

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Highlights? Tet1 facilitates iPSC induction by promoting Oct4 demethylation and reactivation ? Tet1 can replace Oct4 to generate fully pluripotent TSKM iPSCs ? Both 5mC and 5hmC increase on the genome during TSKM 2° reprogramming ? 5hmC promotes the demethylation of pluripotency genes during reprogramming     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation

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Highlights? H2B ubiquitylation directly stimulates H3K4 methylation by the yeast Set1 complex ? Swd2 is not directly required for the H3K4 methylation activity of the yeast Set1 complex ? The Set1 n-SET domain plays a critical role in H2Bub-dependent H3K4 methylation ? Spp1 is conditionally involved in n-SET- and H2Bub-dependent H3K4 methylation