Structural insights into the catalytic mechanism of the AP endonuclease AtARP.

Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification.

Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation.

Oxidative phosphorylation (OXPHOS) consumes oxygen to produce ATP. However, the mechanism that balances OXPHOS activity and intracellular oxygen availability remains elusive. Here, we report that mitochondrial protein lactylation is induced by intracellular hypoxia to constrain OXPHOS.

ESRP1 controls biogenesis and function of a large abundant multiexon circRNA.

While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2-27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing regulator ESRP1. CircDOCK1(2-27) synthesis in epithelial cells represses cell motility both by diverting transcripts from DOCK1 mRNA production to circRNA formation and by direct inhibition of migration by the circRNA.

Structural characterization of an isocytosine-specific deaminase VCZ reveals its application potential in the anti-cancer therapy.

Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction.

Cryo-EM structures of human mA writer complexes.

N-methyladenosine (mA) is the most abundant ribonucleotide modification among eukaryotic messenger RNAs. The mA "writer" consists of the catalytic subunit mA-METTL complex (MAC) and the regulatory subunit mA-METTL-associated complex (MACOM), the latter being essential for enzymatic activity. Here, we report the cryo-electron microscopy (cryo-EM) structures of MACOM at a 3.

Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ.

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms.

Structure Characterization of Pseudouridine Kinase PsuK.

Pseudouridine (Ψ) is one of the most abundant RNA modifications in cellular RNAs that post-transcriptionally impact many aspects of RNA. However, the metabolic fate of modified RNA nucleotides has long been a question. A pseudouridine kinase (PsuK) and a pseudouridine monophosphate glycosylase (PsuG) in were first characterized as involved in pseudouridine degradation by catalyzing the phosphorylation of pseudouridine to pseudouridine 5'-phosphate (ΨMP) and further hydrolyzing 5'-ΨMP to produce uracil and ribose 5'-phosphate.

Structural basis for histone H3 recognition by NASP in Arabidopsis.

The structural basis for histone recognition by the histone chaperone nuclear autoantigenic sperm protein (NASP) remains largely unclear. Here, we showed that Arabidopsis thaliana AtNASP is a monomer and displays robust nucleosome assembly activity in vitro. Examining the structure of AtNASP complexed with a histone H3 α3 peptide revealed a binding mode that is conserved in human NASP.

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase revealed a Cupin fold.

Nucleotides metabolism is a fundamental process in all organisms. Two families of nucleoside phosphorylases (NP) that catalyze the phosphorolytic cleavage of the glycosidic bond in nucleosides have been found, including the trimeric or hexameric NP-I and dimeric NP-II family enzymes. Recent studies revealed another class of NP protein in Escherichia coli named Pyrimidine/purine nucleoside phosphorylase (ppnP), which can catalyze the phosphorolysis of diverse nucleosides and yield d-ribose 1-phosphate and the respective free bases.

Comprehensive Analysis of the Expression and Prognosis for MMPs in Human Colorectal Cancer.

Background: Previous study implicated that genes of matrix metalloproteinase (MMP) family play an important role in tumor invasion, neoangiogenesis, and metastasis. However, the diverse expression patterns and prognostic values of 24 MMPs in colorectal cancer are yet to be analyzed.

Methods: In this study, by integrating public database and our data, we first investigated the expression levels and protein levels of MMPs in patients with colorectal cancer.

Structural basis for anti-CRISPR repression mediated by bacterial operon proteins Aca1 and Aca2.

It has been shown that phages have evolved anti-CRISPR (Acr) proteins to inhibit host CRISPR-Cas systems. Most acr genes are located upstream of anti-CRISPR-associated (aca) genes, which is instrumental for identifying these acr genes. Thus far, eight Aca families (Aca1-Aca8) have been identified, all proteins of which share low sequence homology and bind to different target DNA sequences.

CPSF30-L-mediated recognition of mRNA mA modification controls alternative polyadenylation of nitrate signaling-related gene transcripts in Arabidopsis.

N-methyladenosine (mA), a ubiquitous internal modification of eukaryotic mRNAs, plays a vital role in almost every aspect of mRNA metabolism. However, there is little evidence documenting the role of mA in regulating alternative polyadenylation (APA) in plants. APA is controlled by a large protein-RNA complex with many components, including CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30).

Author Correction: Chiral recognition and enantiomer excess determination based on emission wavelength change of AIEgen rotor.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Enhanced DNA Sensing and Chiroptical Performance by Restriction of Double-Bond Rotation of AIE -Tetraphenylethylene Macrocycle Diammoniums.

The aggregation-induced emission (AIE) mechanism of restriction of double-bond rotation (RDBR) was utilized to design an excellent solid emitter and sensor for the first time. Thus, -tetraphenylethylene (TPE) macrocycle diammoniums were synthesized and bound to a DNA chain by its two ammonium arms. The formed TPE dicycle at the position restricted the rotation of the double bond in both the ground and excited states, resulting in AIE enhancement, chiroptical performance enhancement, and sensing enhancement.

Chiral recognition and enantiomer excess determination based on emission wavelength change of AIEgen rotor.

Chiral recognition, such as enantioselective interactions of enzyme with chiral agents, is one of the most important issues in the natural world. But artificial chiral receptors are much less efficient than natural ones. For tackling the chiral recognition and enantiomer excess (ee) analysis, up until now all the fluorescent receptors have been developed based on fluorescence intensity changes.

Molecular basis of abasic site sensing in single-stranded DNA by the SRAP domain of E. coli yedK.

HMCES and yedK were recently identified as sensors of abasic sites in ssDNA. In this study, we present multiple crystal structures captured in the apo-, nonspecific-substrate-binding, specific-substrate-binding, and product-binding states of yedK. In combination with biochemical data, we unveil the molecular basis of AP site sensing in ssDNA by yedK.

Structure of -methyl-AMP deaminase ADAL with bound GMP and IMP and implications for -methyl-AMP recognition and processing.

aminohydrolase (ADAL) has been shown to be involved in the metabolism of N-methyl-AMP, a proposed intermediate during mA-modified RNA metabolism, which can be subsequently incorporated into newly synthesized RNA by Pol II. It has been proposed that ADAL will prevent N-methyl-AMP reuse and catabolize it to inosine monophosphate (IMP). Here, we have solved the crystal structures of ADAL in the apo form and in complex with GMP and IMP in the presence of Zn.

DNA methylation repels targeting of Arabidopsis REF6.

RELATIVE OF EARLY FLOWERING 6 (REF6/JMJ12), a Jumonji C (JmjC)-domain-containing H3K27me3 histone demethylase, finds its target loci in Arabidopsis genome by directly recognizing the CTCTGYTY motif via its zinc-finger (ZnF) domains. REF6 tends to bind motifs located in active chromatin states that are depleted for heterochromatic modifications. However, the underlying mechanism remains unknown.

Ribonuclease activity of MARF1 controls oocyte RNA homeostasis and genome integrity in mice.

Producing normal eggs for fertilization and species propagation requires completion of meiosis and protection of the genome from the ravages of retrotransposons. Mutation of (meiosis regulator and mRNA stability factor 1) results in defects in both these key processes in mouse oocytes and thus in infertility. MARF1 was predicted to have ribonuclease activity, but the structural basis for the function of MARF1 and the contribution of its putative ribonuclease domain to the mutant oocyte phenotype was unknown.

Structural basis for multiple gene regulation by human DUX4.

DUX4 plays critical role in the molecular pathogenesis of the neuromuscular disorder facioscapulohumeral muscular dystrophy and acute lymphoblastic leukemia in humans. As a master transcription regulator, DUX4 can also bind the promoters and activate the transcription of hundreds ZGA-associated genes. Here we report on the structural and biochemical studies of DUX4 double homeodomains (DUX4-DH), representing the only structures contain both homeodomain 1 (HD1) and homeodomain 2 (HD2).

High-resolution DNA quadruplex structure containing all the A-, G-, C-, T-tetrads.

DNA can form diverse structures, which predefine their physiological functions. Besides duplexes that carry the genetic information, quadruplexes are the most well-studied DNA structures. In addition to their important roles in recombination, replication, transcription and translation, DNA quadruplexes have also been applied as diagnostic aptamers and antidisease therapeutics.

Structural insight into the role of VAL1 B3 domain for targeting to FLC locus in Arabidopsis thaliana.

Vernalization is a pivotal stage for some plants involving many epigenetic changes during cold exposure. In Arabidopsis, an essential step in vernalization for further flowering is successful silence the potent floral repressor Flowering Locus C (FLC) by repressing histone mark. AtVal1 is a multi-function protein containing five domains that participate into many recognition processes and is validated to recruit the repress histone modifier PHD-PRC2 complex and interact with components of the ASAP complex target to the FLC nucleation region through recognizing a cis element known as CME (cold memory element) by its plant-specific B3 domain.