Distribution of microplastics in rainfall and their control by a permeable pavement in low-impact development facility.

Microplastics (MPs) released from plastic products in daily life are present in the air and could be transported to freshwater environments along with rain. Recently, low-impact development (LID) facilities, such as permeable pavements, have been used to treat non-point source pollutants, including rainfall runoff. While runoff is treated by LID facilities, the periodic monitoring of MPs in rainfall and the efficiency of removal of MPs through LID facilities have rarely been investigated.

Prediction of Prognosis in Pancreatic Cancer According to Methionyl-tRNA Synthetase 1 Expression as Determined by Immunohistochemical Staining.

The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)-which facilitates cancer growth by modulating protein synthesis and the cell cycle-to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery.

AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis.

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation.

Allosteric Inhibition of the Tumor-Promoting Interaction Between Exon 2-Depleted Splice Variant of Aminoacyl-Transfer RNA Synthetase-Interacting Multifunctional Protein 2 and Heat Shock Protein 70.

Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound ) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2-depleted splice variant of aminoacyl-transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound binds to the N-terminal subdomain of glutathione -transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies.

Structural basis for the dynamics of human methionyl-tRNA synthetase in multi-tRNA synthetase complexes.

In mammals, eight aminoacyl-tRNA synthetases (AARSs) and three AARS-interacting multifunctional proteins (AIMPs) form a multi-tRNA synthetase complex (MSC). MSC components possess extension peptides for MSC assembly and specific functions. Human cytosolic methionyl-tRNA synthetase (MRS) has appended peptides at both termini of the catalytic main body.

Cell-based analysis of pairwise interactions between the components of the multi-tRNA synthetase complex.

Cytoplasmic aminoacyl-tRNA synthetases (ARSs) are organized into multi-tRNA synthetase complexes (MSCs), from Archaea to mammals. An evolutionary conserved role of the MSCs is enhancement of aminoacylation by forming stable associations of the ARSs and tRNAs. In mammals, a single macromolecular MSC exists, which is composed of eight cytoplasmic ARSs, for nine amino acids, and three scaffold proteins.

Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16-Negative Cancer.

Although abnormal increases in the level or activity of cyclin-dependent kinase 4 (CDK4) occur frequently in cancer, the underlying mechanism is not fully understood. Here, we show that methionyl-tRNA synthetase (MRS) specifically stabilizes CDK4 by enhancing the formation of the complex between CDK4 and a chaperone protein. Knockdown of MRS reduced the CDK4 level, resulting in G0/G1 cell cycle arrest.

High-Throughput Screening for Protein Synthesis Inhibitors Targeting Aminoacyl-tRNA Synthetases.

Aminoacylation has been implicated in a wide variety of cancers. Aminoacyl-tRNA synthetases (ARSs) exist in large excess in tumor cells due to their increased demand for translation, whereas most other protein-synthesis apparatuses are quantitatively limited. Among other components that constitute the translation machinery-namely, tRNA, amino acid, ATP, and ARS-ARS is the only target that can be blocked by small molecules.

Transfer-RNA-mediated enhancement of ribosomal proteins S6 kinases signaling for cell proliferation.

While transfer-RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA and was independent to mTOR (mammalian target of rapamycin) signaling.

The RNA polymerase II C-terminal domain-interacting domain of yeast Nrd1 contributes to the choice of termination pathway and couples to RNA processing by the nuclear exosome.

The RNA polymerase II (RNApII) C-terminal domain (CTD)-interacting domain (CID) proteins are involved in two distinct RNApII termination pathways and recognize different phosphorylated forms of CTD. To investigate the role of differential CTD-CID interactions in the choice of termination pathway, we altered the CTD-binding specificity of Nrd1 by domain swapping. Nrd1 with the CID from Rtt103 (Nrd1(CID(Rtt103))) causes read-through transcription at many genes, but can also trigger termination where multiple Nrd1/Nab3-binding sites and the Ser(P)-2 CTD co-exist.