Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding

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Highlights? The AF9 AHD is intrinsically disordered ? The AHD recruits AF4, BCoR, Dot1L, and hPC3 by coupled folding and binding ? AF9 binding partners compete for binding to a common site ? Dynamics of the AF4-AF9 complex may facilitate exchange between partners     

Structure of the MST4 in Complex with MO25 Provides Insights into Its Activation Mechanism

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Highlights? MO25 forms a stable complex with MST4 to enhance its kinase activity ? Association of MO25 activates MST4 by rotating its αC helix to active conformation ? Kinase-domain-mediated dimerization is required for MST4 trans-autophosphorylation ? MO25-stimulated activation of MST4 promotes apoptosis in HEK293T cells     

ASH2L Regulates Ubiquitylation Signaling to MLL: trans-Regulation of H3 K4 Methylation in Higher Eukaryotes

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Highlights? ASH2L WH motif is important for trans-regulation of H3 K4 methylation by H2Bub ? Ub stimulates MLL activity in trans, in contrast to DOT1L regulation by H2Bub ? H2Bub enhances MLL, but not MLL3, methyltransferase activity ? H2Aub directly represses MLL methyltransferase activity     

Moderation of Arabidopsis Root Stemness by CLAVATA1 and ARABIDOPSIS CRINKLY4 Receptor Kinase Complexes

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Highlights? CLV1 receptor kinase regulates stemness in Arabidopsis root and shoot meristems ? CLV1 and ACR4 form homo- and heteromeric complexes as shown by a novel FRET assay ? CLV1/ACR4 complexes differ in composition between plasma membrane and plasmodesmata ? CLV1/ACR4 complexes regulate distal root meristem maintenance     

hnRNP A1 proofreads 3' splice site recognition by U2AF

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Highlights? hnRNP A1 displaces U2AF from uridine-rich RNAs not followed by a 3′ splice site AG ? A 3′ splice site AG allows formation of a ternary complex with hnRNP A1 and U2AF ? AG proofreading requires U2AF35 and the glycine-rich domain of hnRNP A1 ? hnRNP A1-mediated proofreading influences U2 snRNP recruitment     

ELF4 Regulates GIGANTEA Chromatin Access through Subnuclear Sequestration

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Highlights? GI forms dynamic subnuclear structures ? GI and ELF4 physically interact at nuclear bodies ? ELF4 regulates subnuclear localization of GI ? ELF4 sequesters GI to nuclear bodies from the CO promoter     

ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation

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Highlights? Induction of ZNF750 expression is necessary for terminal epidermal differentiation ? The C2H2 domain of ZNF750 is necessary for its prodifferentiation function ? p63 is necessary for the induction of ZNF750 expression during differentiation ? ZNF750 activates the expression of KLF4 to drive differentiation gene expression     

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     

Impaired KLHL3-Mediated Ubiquitination of WNK4 Causes Human Hypertension

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Highlights? WNK4 kinase is a substrate of KLHL3-Cullin3-targeted ubiquitination ? PHAII-causing mutations of WNK4, KLHL3, and Cullin3 decrease WNK4 ubiquitination ? Impaired WNK4 ubiquitination activates the OSR1/SPAK-NCC axis and causes hypertension     

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     

Genetic Correction of a LRRK2 Mutation in Human iPSCs Links Parkinsonian Neurodegeneration to ERK-Dependent Changes in Gene Expression

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Highlights? hiPSC-derived neurons with LRRK2 G2019S exhibit Parkinsonian neurodegeneration ? Genetic correction of the LRRK2 mutation rescued neurodegenerative phenotypes ? Comparative analysis links LRRK2 G2019S, gene dysregulation, and ERK activation ? ERK-dependent gene dysregulation by LRRK2 G2019S contributes to neurodegeneration     

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     

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

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Highlights? c-Src phosphorylates syndecan-4 in response to extracellular stimuli ? Syndecan-4 phosphorylation and engagement regulate Arf6 activity ? Syndecan-4-mediated Arf6 activity regulates differential integrin recycling ? Syndecan-4-mediated integrin recycling controls FA dynamics and cell migration     

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     

A Major Epigenetic Programming Mechanism Guided by piRNAs

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Highlights? Piwi-piRNA complexes bind to numerous piRNA-complementary sequences in the genome ? piRNA is necessary and sufficient to recruit Piwi, HP1, and HMT to its target site ? Piwi deficiency drastically changes the epigenetic landscape in the genome ? The Piwi-piRNA mechanism is a major epigenetic programming mechanism in Drosophila     

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