TRNA maturation consists of the specific removal of precursor sequences from both the 5' and 3' termini of an initial RNA transcript. How this is accomplished has heretofore not been ascertained in any system. Using Northern analysis of RNA isolated from a variety of RNase-deficient E. coli strains, we have identified the processing intermediates that accumulate in the absence of specific processing nucleases. From this information we have established the maturation pathways for 12 different E. coli tRNAs including the specific role of each of the relevant RNases in the process. The surprising conclusion from this work is that tRNA maturation is a stochastic process that lacks a defined order and that can proceed with a variety of alternative 3' processing nucleases.

Enhancer of zeste homolog 2 (EZH2), a key histone methyltransferase and EMT inducer, is overexpressed in diverse carcinomas, including breast cancer. However, the molecular mechanisms of EZH2 dysregulation in cancers are still largely unknown. Here, we discover that EZH2 is asymmetrically dimethylated at R342 (meR342-EZH2) by PRMT1. meR342-EZH2 was found to inhibit the CDK1-mediated phosphorylation of EZH2 at T345 and T487, thereby attenuating EZH2 ubiquitylation mediated by the E3 ligase TRAF6. We also demonstrate that meR342-EZH2 resulted in a decrease in EZH2 target gene expression, but an increase in breast cancer cell EMT, invasion and metastasis. Moreover, we confirm the positive correlations among PRMT1, meR342-EZH2 and EZH2 expression in the breast cancer tissues. Finally, we report that high expression levels of meR342-EZH2 predict a poor clinical outcome in breast cancer patients. Our findings may provide a novel diagnostic target and promising therapeutic target for breast cancer metastasis.

Enhancer of zeste homolog 2 (EZH2), as a main component of Polycomb Repressive Complex 2, catalyzes histone H3K27me3 to silence its target gene expression. EZH2 upregulation results in cancer development and poor prognosis of cancer patients. Post-translational modifications (PTMs) are important biological events in cancer progression. PTMs regulate protein conformation and diversity functions. Recently, mounting studies have demonstrated that EZH2 stability, histone methyltransferase activity, localization, and binding partners can be regulated by PTMs, including phosphorylation,O-GlcNAcylation, acetylation, methylation and ubiquitination. However, the detailed molecular mechanisms of the EZH2-PTMs and whether other types of PTMs occur in EZH2 remain largely unclear. This review presents an overview of different roles of EZH2 modification and EZH2-PTMs crosstalk during tumorigenesis and cancer metastasis. We also discussed the therapeutic potential of targeting EZH2 modifications for cancer therapy.

Many types of cancer cells, including colorectal cancer cells (CRC), can simultaneously enhance glycolysis and repress the mitochondrial tricarboxylic acid (TCA) cycle, which is called the Warburg effect. However, the detailed mechanisms of abnormal activation of the glycolysis pathway in colorectal cancer are largely unknown. In this study, we reveal that the protein arginine methyltransferase 1 (PRMT1) promotes glycolysis, proliferation, and tumorigenesis in CRC cells. Mechanistically, PRMT1-mediated arginine asymmetric dimethylation modification of phosphoglycerate kinase 1 (PGK1, the first ATP-producing enzyme in glycolysis) at R206 (meR206-PGK1) enhances the phosphorylation level of PGK1 at S203 (pS203-PGK1), which inhibits mitochondrial function and promotes glycolysis. We found that PRMT1 and meR206-PGK1 expression were positively correlated with pS203-PGK1 expression in tissues from colorectal cancer patients. Furthermore, we also confirmed that meR206-PGK1 expression is positively correlated with the poor survival of patients with colorectal cancer. Our findings show that PRMT1 and meR206-PGK1 may become promising predictive biomarkers for the prognosis of patients with CRC and that arginine methyltransferase inhibitors have great potential in colorectal cancer treatment.

Protein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.