The emerging role of deubiquitylating enzyme USP21 as a potential therapeutic target in cancer.

Although certain members of the Ubiquitin-specific peptidases (USPs) have been recognized as promising therapeutic targets for various diseases, research progress regarding USP21 has been relatively sluggish in its early stages. USP21 is a crucial member of the USPs subfamily, involved in diverse cellular processes such as apoptosis, DNA repair, and signal transduction. Research findings from the past decade demonstrate that USP21 mediates the deubiquitination of multiple well-known target proteins associated with critical cellular processes relevant to both disease and homeostasis, particularly in various cancers.This reviewcomprehensively summarizes the structure and biological functions of USP21 with an emphasis on its role in tumorigenesis, and elucidates the advances on the discovery of tens of small-molecule inhibitors targeting USP21, which suggests that targeting USP21 may represent a potential strategy for cancer therapy.

A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.

Breast cancer (BC) is a kind of malignant cancer in women, and it has become the most diagnosed cancer worldwide since 2020. Histone methylation is a common biological epigenetic modification mediating varieties of physiological and pathological processes. Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression. It is also specifically amplified in breast cancer and contributes to BC tumorigenesis and drug resistance via both demethylase and non-demethylase manners. This review will provide insight into the overview structure of LSD1, summarize its action mechanisms in BC, describe the therapeutic potential of LSD1 inhibitors in BC, and prospect the current opportunities and challenges of targeting LSD1 for BC therapy.

Characterization of Imprinted Genes in Rice Reveals Conservation of Regulation and Imprinting with Other Plant Species.

Genomic imprinting is an epigenetic phenomenon by which certain genes display differential expression in a parent-of-origin-dependent manner. Hundreds of imprinted genes have been identified from several plant species. Here, we identified, with a high level of confidence, 208 imprinted gene candidates from rice (Oryza sativa). Imprinted genes of rice showed limited association with the transposable elements, which contrasts with findings from Arabidopsis (Arabidopsis thaliana). Generally, imprinting in rice is conserved within a species, but intraspecific variation also was detected. The imprinted rice genes do not show signatures of selection, which suggests that domestication has had a limited evolutionary consequence on genomic imprinting. Although conservation of imprinting in plants is limited, we show that some loci are imprinted in several different species. Moreover, our results suggest that different types of epigenetic regulation can be established either before or after fertilization. Imprinted 24-nucleotide small RNAs and their neighboring genes tend to express alleles from different parents. This association was not observed between 21-nucleotide small RNAs and their neighboring genes. Together, our findings suggest that the regulation of imprinting can be diverse, and genomic imprinting has evolutionary and biological significance.

Whole genome sequence of Pseudomonas aeruginosa F9676, an antagonistic bacterium isolated from rice seed.

Pseudomonas aeruginosa is a group of bacteria, which can be isolated from diverse ecological niches. P. aeruginosa strain F9676 was first isolated from a rice seed sample in 2003. It showed strong antagonism against several plant pathogens. In this study, whole genome sequencing was carried out. The total genome size of F9676 is 6368,008bp with 5586 coding genes (CDS), 67 tRNAs and 3 rRNAs. The genome sequence of F9676 may shed a light on antagonism P. aeruginosa.

A Rare Allele of GS2 Enhances Grain Size and Grain Yield in Rice.

Grain size determines grain weight and affects grain quality. Several major quantitative trait loci (QTLs) regulating grain size have been cloned; however, our understanding of the underlying mechanism that regulates the size of rice grains remains fragmentary. Here, we report the cloning and characterization of a dominant QTL, grain size on chromosome 2 (GS2), which encodes Growth-Regulating Factor 4 (OsGRF4), a transcriptional regulator. GS2 localizes to the nucleus and may act as a transcription activator. A rare mutation of GS2 affecting the binding site of a microRNA, OsmiR396c, causes elevated expression of GS2/OsGRF4. The increase in GS2 expression leads to larger cells and increased numbers of cells, which thus enhances grain weight and yield. The introduction of this rare allele of GS2/OsGRF4 into rice cultivars could significantly enhance grain weight and increase grain yield, with possible applications in breeding high-yield rice varieties.

Identification and characterization of Mini1, a gene regulating rice shoot development.

The aerial parts of higher plants are generated from the shoot apical meristem (SAM). In this study, we isolated a small rice (Oryza sativa L.) mutant that showed premature termination of shoot development and was named mini rice 1 (mini1). The mutant was first isolated from a japonica cultivar Zhonghua11 (ZH11) subjected to ethyl methanesulfonate (EMS) treatment. With bulked segregant analysis (BSA) and map-based cloning method, Mini1 gene was finally fine-mapped to an interval of 48.6 kb on chromosome 9. Sequence analyses revealed a single base substitution from G to A was found in the region, which resulted in an amino acid change from Gly to Asp. The candidate gene Os09g0363900 was predicted to encode a putative adhesion of calyx edges protein ACE (putative HOTHEAD precursor) and genetic complementation experiment confirmed the identity of Mini1. Os09g0363900 contains glucose-methanol-choline (GMC) oxidoreductase and NAD(P)-binding Rossmann-like domain, and exhibits high similarity to Arabidopsis HOTHEAD (HTH). Expression analysis indicated Mini1 was highly expressed in young shoots but lowly in roots and the expression level of most genes involved in auxin biosynthesis and signal transduction were reduced in mutant. We conclude that Mini1 plays an important role in maintaining SAM activity and promoting shoot development in rice.

A point mutation in the zinc finger motif of RID1/EHD2/OsID1 protein leads to outstanding yield-related traits in japonica rice variety Wuyunjing 7.

BACKGROUND: Flowering time, which is often associated with the length of the growth period in rice, determines the adaptability of a plant to various environments. However, little is known about how flowering-time genes affect panicle development and yield formation potential in rice after inducing the transition from vegetative growth to reproductive growth. RESULTS: To explore the relationship between floral induction and yield formation and the molecular mechanism of panicle development in rice, a novel mutant, ghd10, was identified from japonica variety Wuyunjing 7 plants subjected to ethyl methane sulfonate (EMS) treatment. The ghd10 mutant exhibited delayed flowering time, tall stalks and increased panicle length and primary branch number. Map-based cloning revealed that Ghd10 encodes a transcription factor with Cys-2/His-2-type zinc finger motifs. Ghd10 is orthologous to INDETERMINATE1 (ID1), which promotes flowering in maize (Zea mays) and is identical to the previously cloned genes Rice Indeterminate1 (RID1), Early heading date2 (Ehd2) and OsId1. Transient expression analysis of the Ghd10-GFP fusion protein in tobacco mesophyll cells showed that this protein is expressed in the nucleus. Ghd10 mRNA accumulated most abundantly in developing leaves and panicle structures, but rarely in roots. Expression analysis revealed that the expression levels of Ehd1, Hd1, RFT1, Hd3a and OsMADS15 decreased dramatically under both short-day and long-day conditions in ghd10. CONCLUSION: These results indicate that Ghd10, which encodes a promoter of flowering, influences plant height and panicle development by regulating the expression levels of some flowering-related genes, such as Ehd1, Hd1, OsMADS15 and others. The ghd10 allele is a useful resource for improvement of panicle traits in rice grown in tropical and low-latitude areas.