P-body及其与mRNA的转录后调节之间的关系

mRNA在真核生物基因表达的转录后调控中发挥着重要作用.然而最新研究发现,一种被命名为P-body胞浆复合体是mRNA转录后调控过程中的一个重要场所,在基因表达过程中起到了至关重要的调控作用.该复合体富含多种功能的蛋白,同时还有细胞因子与RNA等成分组成,其功能特征为参与mRNA降解、翻译抑制、mRNA监视以及RNA介导基因沉默等重要生命活动过程.研究发现,P-body是特化的细胞成分.本文详细阐述P-body的发现、结构特征以及与mRNA转录后调控的关系,使人们对P-body的生物学功能有更深入地了解和认识,另一方面将有助于更进一步深入探讨基因的表达调节机制.

LSM14B coordinates protein component expression in the P-body and controls oocyte maturation

The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be studied.Here,we demonstrate that Smith-like(LSM)family member 14B(LSM14B)regulates oocyte maturation,and the loss of LSM14B in mouse ovaries leads to abnormal oocyte MII arrest and female infertility.Next,we find the aberrant transcriptional activation,indicated by abnormal non-surrounded nucleolus and surrounded nucleolus oocyte proportions,and abnormal chromosome assembly and segregation in Lsm14b-deficient mouse oocytes.The global transcriptome analysis suggests that many transcripts involved in cytoplasmic processing body(P-body)function are altered in Lsm14b-deficient mouse oocytes.Deletion of Lsm14b results in the expression and/or localization changes of P-body components(such as LSM14A,DCP1A,and 4E-T).Notably,DDX6,a key component of the P-body,is downregulated and accumulates in the nuclei in Lsm14b-deficient mouse oocytes.Taken together,our data suggest that LSM14B links mouse oocyte maturation to female fertility through the regulation of the P-body.

Exogenous nucleic acids aggregate in non-P-body cytoplasmic granules when transfected into cultured cells

To modulate gene expression in research studies or in potential clinical therapies,transfection of exogenous nucleic acids including plasmid DNA and small interference RNA(siRNA)are generally performed.However,the cellular processing and the fate of these nucleic acids remain elusive.By investigating the cellular behavior of transfected nucleic acids using confocal imaging,here we show that when siRNA was cotransfected into cultured cells with other nucleic acids,including single-stranded RNA oligonucleotides,single and double-stranded DNA oligonucleotides,as well as long double-stranded plasmid DNA,they all aggregate in the same cytoplasmic granules.Interestingly,the amount of siRNA aggregating in granules was found not to correlate with the gene silencing activity,suggesting that assembly of cytoplasmic granules triggered by siRNA transfection may be separable from the siRNA silencing event.Our results argue against the claim that the siRNAaggregating granules are the functional site of RNA interference(RNAi).Taken together,our studies suggest that,independent of their types or forms,extraneously transfected nucleic acids are processed through a common cytoplasmic pathway and trigger the formation of a new type of cytoplasmic granules“transfection granules”.

中国科学家在乙烯信号转导领域取得突破性进展

乙烯是一种气态植物激素,在植物生长发育的各个阶段发挥着非常重要的作用。最近,中国科学家在乙烯信号转导的分子机制研究中取得了突破性进展。

Viral Regulation of RNA Granules in Infected Cells

RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules(SG) and GW182/DCP-specific RNA processing bodies(PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude m RNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.

The role of the CNOT1 subunit of the CCR4-NOT complex in mRNA deadenylation and cell viability

The human CCR4-NOT deadenylase complex consists of at least nine enzymatic and non-enzymatic subunits.Accumulating evidence suggests that the non-enzymatic subunits are involved in the regulation of mRNA deadenylation,although their precise roles remain to be established.In this study,we addressed the function of the CNOT1 subunit by depleting its expression in HeLa cells.Flow cytometric analysis revealed that the sub G1 fraction was increased in CNOT1-depleted cells.Virtually,the same level of the sub G1 fraction was seen when cells were treated with a mixture of siRNAs targeted against all enzymatic subunits,suggesting that CNOT1 depletion induces apoptosis by destroying the CCR4-NOT-associated deadenylase activity.Further analysis revealed that CNOT1 depletion leads to a reduction in the amount of other CCR4-NOT subunits.Importantly,the specific activity of the CNOT6L immunoprecipitates-associated deadenylase from CNOT1-depleted cells was less than that from control cells.The formation of P-bodies,where mRNA decay is reported to take place,was largely suppressed in CNOT1-depleted cells.Therefore,CNOT1 has an important role in exhibiting enzymatic activity of the CCR4-NOT complex,and thus is critical in control of mRNA deadenylation and mRNA decay.We further showed that CNOT1 depletion enhanced CHOP mRNA levels and activated caspase-4,which is associated with endoplasmic reticulum ER stress-induced apoptosis.Taken together,CNOT1 depletion structurally and functionally deteriorates the CCR4-NOTcomplex and induces stabilization of mRNAs,which results in the increment of translation causing ER stress-mediated apoptosis.We conclude that CNOT1 contributes to cell viability by securing the activity of the CCR4-NOT deadenylase.