Endogenous RBM4 prevents Ang II-induced cardiomyocyte hypertrophy via downregulating the expression of PTBP1.

Aberrant gene expression in cardiomyocyte has been revealed to be the fundamental essence of pathological cardiac hypertrophy. However, the detailed mechanisms are not fully understood. The underlying regulators of gene expression involved in cardiac hypertrophy remain to be further identified. Here, we report that the RNA-binding protein RNA-binding motif protein 4 (RBM4) functions as an endogenic protector that is able to fight against cardiomyocyte hypertrophy in vitro. Under pro-hypertrophic stimulation of angiotensin II (Ang II), the protein level of RBM4 in cardiomyocyte and myocardium is elevated. Knockdown of RBM4 can further aggravate cardiomyocyte hypertrophy, while over-expression of RBM4 represses cardiomyocyte hypertrophy. Mechanistically, RBM4 is localized in the nucleus and down-regulates the expression of polypyrimidine tract-binding protein 1 (PTBP1), which has been shown to aggravate cardiomyocyte hypertrophy. In addition, we suggest that the up-regulation of RBM4 in cardiomyocyte hypertrophy is caused by N6-methyladenosine (m6A). Ang II induces m6A methylation of RBM4 mRNA, which further enhances the YTH domain-containing family protein 1 (YTHDF1)-mediated translation of RBM4. Thus, our results reveal a novel pathway consisting of m6A, RBM4 and PTBP1, which is involved in cardiomyocyte hypertrophy.

Circular RNA-circLRP6 protects cardiomyocyte from hypoxia-induced apoptosis by facilitating hnRNPM-mediated expression of FGF-9.

Coronary atherosclerosis-induced myocardial ischemia leads to cardiomyocyte apoptosis. The regulatory mechanisms for cardiomyocyte apoptosis have not been fully understood. Circular RNAs are non-coding RNAs which play important roles in heart function maintenance and progression of heart diseases by regulating gene transcription and protein translation. Here, we reported a conserved cardiac circular RNA, which is generated from the second exon of LRP6 and named circLRP62-2 . CircLRP62-2 can protect cardiomyocyte from hypoxia-induced apoptosis. The expression of circLRP62-2 in cardiomyocytes was down-regulated under hypoxia, while forced expression of circLRP62-2 inhibited cell apoptosis. Normally, circLRP62-2 was mainly localized in the nucleus. Under hypoxia, circLRP62-2 is associated with heterogeneous nuclear ribonucleoprotein M (hnRNPM) to be translocated into the cytoplasm. It recruited hnRNPM to fibroblast growth factor 9 (FGF9) mRNA to enhance the expression of FGF9 protein, promoting hypoxia-adaption and viability of cardiomyocytes. In summary, this study uncovers a new inhibitor of apoptosis and reveals a novel anti-apoptotic pathway composed of circLRP62-2 , hnRNPM, and FGF9, which may provide therapeutic targets for coronary heart disease and ischemic myocardial injury.

Mitochondrial Non-Coding RNAs Are Potential Mediators of Mitochondrial Homeostasis.

Mitochondria are the energy production center in cells, which regulate aerobic metabolism, calcium balance, gene expression and cell death. Their homeostasis is crucial for cell viability. Although mitochondria own a nucleus-independent and self-replicating genome, most of the proteins, which fulfill mitochondrial functions and mitochondrial quality control, are encoded by the nuclear genome and are imported into mitochondria. Hence, the regulation of mitochondrial protein expression and translocation is considered essential for mitochondrial homeostasis. By means of high-throughput RNA sequencing and bioinformatic analysis, non-coding RNAs localized in mitochondria have been generally identified. They are either generated from the mitochondrial genome or the nuclear genome. The mitochondrial non-coding RNAs can directly interact with mitochondrial DNAs or transcripts to affect gene expression. They can also bind nuclear genome-encoded mitochondrial proteins to regulate their mitochondrial import, protein level and combination. Generally, mitochondrial non-coding RNAs act as regulators for mitochondrial processes including oxidative phosphorylation and metabolism. In this review, we would like to introduce the latest research progressions regarding mitochondrial non-coding RNAs and summarize their identification, biogenesis, translocation, molecular mechanism and function.

Integrated production of bio-jet fuel containing lignin-derived arenes via lipid deoxygenation.

We report an integrated production of bio-jet fuel, from dehydrogenation of lignin-derived cycloalkanes and deoxygenation of lipid over PtIr/γ-Al2O3 at 400 °C in the absence of hydrogen. The CO generated in situ via lipid decarbonylation is strongly adsorbed by Ir and subsequently undergoes methanation, with the remaining Pt sites catalyzing cycloalkane dehydrogenation.