Polycomb proteins RING1A/B promote H2A monoubiquitination to regulate female gametophyte development in Arabidopsis.

A functional female gametophyte is the basis of successful sexual reproduction in flowering plants. During female gametophyte development, the megaspore mother cell (MMC), differentiated from a single subepidermal somatic cell in the nucellus, undergoes meiosis to produce four megaspores; only the one at the chalazal end, referred to as functional megaspore (FM), undergoes three rounds of mitosis and develops into a mature embryo sac. Here, we reported that RING1A and RING1B (RING1A/B), two functionally redundant Polycomb proteins in Arabidopsis, are critical for female gametophyte development. The mutations of RING1A/B resulted in defects in MMC and FM's specification and subsequent mitosis of FM, thereby leading to aborted ovules. Gene expression analysis revealed several genes essential for female gametophyte development, including Argonaute (AGO) family genes and critical transcription factors, were ectopically expressed in ring1a ring1b. Furthermore, RING1A/B bound some of these genes to promote H2A monoubiquitination (H2Aub) deposition. Together, RING1A/B promote H2Aub modification at genes essential for female gametophyte development, suppressing their expression to ensure the progression of female gametophyte development.

The Histone Variant H3.3 Is Required for Plant Growth and Fertility in Arabidopsis.

Histones are the core components of the eukaryote chromosome, and have been implicated in transcriptional gene regulation. There are three major isoforms of histone H3 in Arabidopsis. Studies have shown that the H3.3 variant is pivotal in modulating nucleosome structure and gene transcription. However, the function of H3.3 during development remains to be further investigated in plants. In this study, we disrupted all three H3.3 genes in Arabidopsis. Two triple mutants, h3.3cr-4 and h3.3cr-5, were created by the CRISPR/Cas9 system. The mutant plants displayed smaller rosettes and decreased fertility. The stunted growth of h3.3cr-4 may result from reduced expression of cell cycle regulators. The shorter stamen filaments, but not the fertile ability of the gametophytes, resulted in reduced fertility of h3.3cr-4. The transcriptome analysis suggested that the reduced filament elongation of h3.3cr-4 was probably caused by the ectopic expression of several JASMONATE-ZIM DOMAIN (JAZ) genes, which are the key repressors of the signaling pathway of the phytohormone jasmonic acid (JA). These observations suggest that the histone variant H3.3 promotes plant growth, including rosette growth and filament elongation.

Comparative Mitochondrial Analysis of Cnaphalocrocis exigua (Lepidoptera: Crambidae) and Its Close Relative C. medinalis.

Rice leaffolders are important pests on rice in Asia, Oceania, and Africa, causing serious loss to rice production. There are two main rice leaffolders in China, namely Cnaphalocrocis medinalis (Guenée) and C. exigua (Butler) with the former having the ability of long-distance migration. To reveal the differences in the mitochondrial genomes (mitogenome) between them, we compared the completed mitogenome of C. exigua with three C. medinalis individuals. Although phylogenetic analysis based on the mitogenomic data strongly supported the close relationship between these two species, many differences were still being revealed. The results showed that the mitogenome of C. exigua was shorter in length (15,262 bp) and slight lower in AT content than that of C. medinalis. Except for the different start codons of nad3 and nad6 gene, we also found the cox1 gene had a typical start codon 'ATG' which suggested that the starting position of this gene must be reconsidered in the entire superfamily Pyraloidea. All tRNAs have a typical clover-leaf structure, except for the dihydrouridine (DHU) stem losing of trnS1, which has the atypical anticondon 'TCT' instead of 'GCT' in C. medinalis and most Pyraloidea species. Two intergenic regions (between trnY and cox1, nad3 and trnA) featured by AT repeats were only found in C. medinalis and even rarely appeared in reported Pyraloidea species. Furthermore, regardless of interspecific comparison or intraspecific comparison of these two species, protein coding genes, especially the atp8 genes, had quite different evolutionary rates.

LncRNA-MALAT1-mediated Axl promotes cell invasion and migration in human neuroblastoma.

Overexpression of Axl has been noted to correlate with several human cancers. However, the regulatory mechanisms and effects of Axl in human neuroblastoma development remain unclear. Here, we explore the expression of Axl in neurobalstoma and related upstream regulatory mechanisms of invasion and migration. We found that Axl was overexpressed in metastatic neuroblastoma tissues and positively associated with long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1. Meanwhile, our data suggested that metastasis-associated lung adenocarcinoma transcript 1 upregulated Axl expression in neuroblastoma cells, resulting in cell invasion and migration. Furthermore, we found that targeting Axl by inhibitor R428 significantly suppressed the abilities of tumor cell invasion and migration. In summary, these results suggested that Axl, which is regulated by long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1, may exert great influence on invasion and migration of neuroblastoma.

Correlation between serum exosome derived miR-208a and acute coronary syndrome.

OBJECTIVE: To explore the correlation of miRNAs with clinical characteristics of ACS. METHODS: 50 ACS patients and 50 healthy controls were randomly selected. On the basis of miRNA expression levels, ACS patients were classified as low miRNA expression group (fold change: <3) and high miRNA expression group (≥3). RESULTS: miR-208a expression increased markedly in the serum exosomes of ACS patients, and miR-208a expression in the serum of ACS patients was also significantly higher than that in healthy controls. However, the sensitivity of serum miR-208a was inferior to that of exosome miR-208a. Analysis of clinical characteristics showed the mean age of 500 ACS patients was 62.35±9.70 years, and there were 300 patients in low miR-208a expression group and 200 patients in high miR-208a expression group. When compared with low miR-208a expression group, patients with high miR-208a expression were older, and had higher Killip class, higher CK-MB peak, higher cTnT peak and elevated LDL (P<0.05). Within 1-year follow up, 32 patients died including 10 in low miR-208a expression group with the mortality of 3.3% and 22 in high miR-208a expression group with the mortality of 11.0%. Kaplan-Meier survival analysis revealed that the 1-year survival rate reduced significantly in patients with high miR-208a expression. CONCLUSION: miRNA-208a expression is significantly up-regulated in the serum exosomes of ACS patients and is crucial for the diagnosis of ACS.

Atorvastatin up-regulates TRIB3 independent of ATF4-CHOP pathway in atherosclerotic patients.

BACKGROUND: Macrophage apoptosis triggered by endoplasmic reticulum (ER) stress contributes much to atherosclerosis, especially plaque vulnerability. Activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)-Tribbles 3 (TRIB3) pathway is closely related to the ER stress. This study aimed to investigate the effect of atorvastatin on the ATF4-CHOP-TRIB3 pathway. METHODS: Forty-seven patients were randomized into 80-mg and 20-mg atorvastatin group. Follow-up was performed at weeks 6 and 12, and complete blood chemistry, lipid assay and detection of 5 target genes (tumor protein 53, ATF4, C/EBP, CHOP and TRIB3) in monocytes/macrophages were conducted. Furthermore, the interaction between dosage and duration of therapy was evaluated. RESULTS: After 12-week therapy, patients in both groups experienced significant reductions in ATF4 (P=0.038) and C/EBP (P=0.003) expressions. Tumor protein 53 (P=0.015) and TRIB3 (P=0.045) expressions increased markedly in 80-mg atorvastatin group. However, there was no significant difference in CHOP expression at three time-points and between atorvastatin groups. Moreover, there was no interaction between dosage and duration of therapy. CONCLUSIONS: Atorvastatin has an effect on ER stress through ATF4-CHOP pathway. Atorvastatin at a high dose is more likely to increase TRIB3 expression, but this warrants further investigation.