Recent studies on enzymes regulating dynamic N6-methyl-adenosine (m6A) in RNA together with the findings from m6A-methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq/m6A- seq) have...Recent studies on enzymes regulating dynamic N6-methyl-adenosine (m6A) in RNA together with the findings from m6A-methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq/m6A- seq) have revealed a broad biological role of m6A in RNA processing, development, differentiation, metabolism and fertility. RNA m6A methylation is catalyzed by a multi- component methyltransferase complex composed of at least three subunits: METTL3, METTL14 and Wilms tumor 1-associated protein (WTAP), in which METTL3 and METTL14 serve as catalytic subunits, while WTAP as reg- ulatory subunit. Dioxygenases FTO and ALKBH5, as the first two known m6A demethylases, catalyze m6A removal. Five m6A-binding proteins are classified into cytoplasmic YT521-B homology (YTH) domain-containing family YT- HDF1-3 and nuclear YTHDC1-2. Perturbation of enzy- matic activities catalyzing dynamic m6A results in altered expression of thousands of genes and affects mRNA stability and splicing at the cellular level. Here, we summarize recent discoveries about m6A methyltransferases (writers),demethylases (erasers) and binding proteins (readers), and further discuss the potential impacts of m6A on RNA pro- cessing, especially on mRNA splicing.展开更多
Objective:To examine the effects of modified Shenmai Yin on invigorating vital energy, promoting blood flow, and protection against neural impairment in an endotoxin-induced shock rat model. Methods: Ninety-six SD rat...Objective:To examine the effects of modified Shenmai Yin on invigorating vital energy, promoting blood flow, and protection against neural impairment in an endotoxin-induced shock rat model. Methods: Ninety-six SD rats were randomly divided into four groups: sham operation (saline 20 ml/kg), shock model (lipopolysaccharide, LPS, 8 mg/kg), Reformed Shengmai Yin (加味生脉饮 Pulse-activating Decoction) (LPS 8 mg/kg + reformed Shengmai Yin Injection 10 ml/kg), and dexamethasone (LPS 8 mg/kg + dexamethasone 5 mg/kg) groups. Each group was subdivided into 1 h, 2 h, 3 h, and 6 h time points for observation. The carotid artery was separated and connected with a biological functional system to monitor mean arterial pressure (MAP). Brain water levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity were also determined. Results: In the shock model group, MAP was progressively decreased after injection of LPS, brain water and MDA contents were increased, brain SOD activity was decreased, and capillary vessel edema in brain tissue was also observed. All these parameters were improved significantly in both treatment groups, although the effects were more marked with Shengmai Yin than with dexamethasone. Conclusion: Modified Shengmai Yin exhibits strong anti-shock and neuroprotective effects against Endotoxininduced shock.展开更多
基金supported by the National BasicResearch Program of China(2011CB510103,2014CB964902)the National Science Foundation of China(91319308,31430022 and31400672)Strategic Priority Research Program of Chinese Academy ofSciences(XDB14030300)
文摘Recent studies on enzymes regulating dynamic N6-methyl-adenosine (m6A) in RNA together with the findings from m6A-methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq/m6A- seq) have revealed a broad biological role of m6A in RNA processing, development, differentiation, metabolism and fertility. RNA m6A methylation is catalyzed by a multi- component methyltransferase complex composed of at least three subunits: METTL3, METTL14 and Wilms tumor 1-associated protein (WTAP), in which METTL3 and METTL14 serve as catalytic subunits, while WTAP as reg- ulatory subunit. Dioxygenases FTO and ALKBH5, as the first two known m6A demethylases, catalyze m6A removal. Five m6A-binding proteins are classified into cytoplasmic YT521-B homology (YTH) domain-containing family YT- HDF1-3 and nuclear YTHDC1-2. Perturbation of enzy- matic activities catalyzing dynamic m6A results in altered expression of thousands of genes and affects mRNA stability and splicing at the cellular level. Here, we summarize recent discoveries about m6A methyltransferases (writers),demethylases (erasers) and binding proteins (readers), and further discuss the potential impacts of m6A on RNA pro- cessing, especially on mRNA splicing.
基金supported by a grant from National Natural Science Foundation of China (No.30672737)
文摘Objective:To examine the effects of modified Shenmai Yin on invigorating vital energy, promoting blood flow, and protection against neural impairment in an endotoxin-induced shock rat model. Methods: Ninety-six SD rats were randomly divided into four groups: sham operation (saline 20 ml/kg), shock model (lipopolysaccharide, LPS, 8 mg/kg), Reformed Shengmai Yin (加味生脉饮 Pulse-activating Decoction) (LPS 8 mg/kg + reformed Shengmai Yin Injection 10 ml/kg), and dexamethasone (LPS 8 mg/kg + dexamethasone 5 mg/kg) groups. Each group was subdivided into 1 h, 2 h, 3 h, and 6 h time points for observation. The carotid artery was separated and connected with a biological functional system to monitor mean arterial pressure (MAP). Brain water levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity were also determined. Results: In the shock model group, MAP was progressively decreased after injection of LPS, brain water and MDA contents were increased, brain SOD activity was decreased, and capillary vessel edema in brain tissue was also observed. All these parameters were improved significantly in both treatment groups, although the effects were more marked with Shengmai Yin than with dexamethasone. Conclusion: Modified Shengmai Yin exhibits strong anti-shock and neuroprotective effects against Endotoxininduced shock.