生物信息学资源助力蛋白质磷酸化的系统层次理解

Protein phosphorylation,catalyzed by protein kinases(PKs),is one of the most prevalent post-translational modifications(PTMs)in eukaryotes.Phosphorylation occurring at different positions in a protein sequence can possess distinct functional impacts,and sitespecific phosphorylation may drastically alter a protein’s conformation,activity,and trafficking.Traditionally,biologists usually focused on studying regulatory mechanisms of phosphorylation in a limited number of proteins,mainly due to a lack of highthroughput technology.During the past two decades,advances in liquid chromatography coupled with tandem mass spectrometry(LC-MS/MC)have boomed a revolutionary technology named phosphoproteomics,which can simultaneously quantify thousands of phosphorylation sites(p-sites),and provide a great opportunity for a systems-level understanding of phosphorylation.Besides LCMS/MC,other approaches such as immunohistochemistry(IHC)and immune-detection by sequencing(ID-seq)have also emerged.

Modelling-based evaluation of the effect of quarantine control by the Chinese government in the coronavirus disease 2019 outbreak

Dear Editor,The recent outbreak of novel coronavirus disease 2019(COVID-19)has already become a global-scale epidemic.Since the case from China was reported on Dec 30th,2019(Huang et al.,2020;Li et al.,2020),the pathogen was soon identified as a new coronavirus on Jan 7th.

Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation

Chronic stress impairs radial neural stem cell(rNSC)differentiation and adult hippocampal neurogenesis(AHN),whereas promoting AHN can increase stress resilience against depression.Therefore,investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs.The nonpsychoactive phytocannabinoid cannabidiol(CBD)has been shown to be effective against depression.However,whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown.Here,by using the chronic restraint stress(CRS)mouse model,we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions.Moreover,transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process.The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte,which was partly mediated by the modulation of the FoxO signaling pathway.These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.

Accurate quantification of 3'-terminal 2'-O-methylated small RNAs by utilizing oxidative deep sequencing and stem-loop RT-qPCR

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive,convenient,and reliable methods for quantifying RNA modifications.In particular,a subset of small RNAs,including microRNAs(miRNAs)and Piwi-interacting RNAs(piRNAs),are modified at their 3'-terminal nucleotides via 2'-0-methylation.However,quantifying the levels of these small RNAs is difficult because 2'-0-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase.These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays.In this study,we profiled 3'-terminal 2'-0-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment.We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach.Likewise,stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-0-methyl piRNAs in human seminal plasma.In summary,this study established a standard procedure for quantifying the levels of 3'-terminal 2'-0-methyl miRNAs in plants and piRNAs.Accurate measurement of the 3'-terminal 2'-0-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.