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Post-transcriptional gene silencing in a dynamic RNP world. 动态RNP世界中的转录后基因沉默。
IF 3.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-25 Print Date: 2023-10-26 DOI: 10.1515/hsz-2023-0203
Simone Larivera, Julia Neumeier, Gunter Meister

MicroRNA (miRNA)-guided gene silencing is a key regulatory process in various organisms and linked to many human diseases. MiRNAs are processed from precursor molecules and associate with Argonaute proteins to repress the expression of complementary target mRNAs. Excellent work by numerous labs has contributed to a detailed understanding of the mechanisms of miRNA function. However, miRNA effects have mostly been analyzed and viewed as isolated events and their natural environment as part of complex RNA-protein particles (RNPs) is often neglected. RNA binding proteins (RBPs) regulate key enzymes of the miRNA processing machinery and furthermore RBPs or readers of RNA modifications may modulate miRNA activity on mRNAs. Such proteins may function similarly to miRNAs and add their own contributions to the overall expression level of a particular gene. Therefore, post-transcriptional gene regulation might be more the sum of individual regulatory events and should be viewed as part of a dynamic and complex RNP world.

微小RNA(miRNA)引导的基因沉默是各种生物体中的一个关键调控过程,与许多人类疾病有关。miRNA由前体分子加工而成,并与Argonaute蛋白结合以抑制互补靶mRNA的表达。许多实验室的出色工作有助于详细了解miRNA的功能机制。然而,miRNA效应大多被分析和视为孤立事件,其作为复杂RNA蛋白颗粒(RNPs)一部分的自然环境往往被忽视。RNA结合蛋白(RBPs)调节miRNA加工机制的关键酶,此外RBPs或RNA修饰的读取器可以调节miRNA在mRNA上的活性。这种蛋白质的功能可能与miRNA类似,并为特定基因的整体表达水平增加其自身的贡献。因此,转录后基因调控可能更多地是单个调控事件的总和,应该被视为动态和复杂的RNP世界的一部分。
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引用次数: 0
Cell-type specific anti-cancerous effects of nitro-oleic acid and its combination with gamma irradiation. 硝基油酸及其与伽马射线照射结合的细胞特异性抗癌作用。
IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-15 Print Date: 2024-03-25 DOI: 10.1515/hsz-2023-0150
Tomas Perecko, Jana Pereckova, Zuzana Hoferova, Martin Falk

Nitro-fatty acids (NFAs) are endogenous lipid mediators capable of post-translational modifications of selected regulatory proteins. Here, we investigated the anti-cancerous effects of nitro-oleic acid (NO2OA) and its combination with gamma irradiation on different cancer cell lines. The effects of NO2OA on cell death, cell cycle distribution, or expression of p21 and cyclin D1 proteins were analyzed in cancer (A-549, HT-29 and FaDu) or normal cell lines (HGF, HFF-1). Dose enhancement ratio at 50 % survival fraction (DERIC50) was calculated for samples pre-treated with NO2OA followed by gamma irradiation. NO2OA suppressed viability and induced apoptotic cell death. These effects were cell line specific but not in general selective for cancer cells. HT-29 cell line exerted higher sensitivity toward NO2OA treatment among cancer cell lines tested: induction of cell cycle arrest in the G2/M phase was associated with an increase in p21 and a decrease in cyclin D1 expression. Pre-treatment of HT-29 cells with NO2OA prior irradiation showed a significantly increased DERIC50, demonstrating radiosensitizing effects. In conclusion, NO2OA exhibited potential for combined chemoradiotherapy. Our results encourage the development of new NFAs with improved features for cancer chemoradiation.

硝基脂肪酸(NFAs)是一种内源性脂质介质,能够对特定的调节蛋白进行翻译后修饰。在此,我们研究了硝基油酸(N2OA)及其与伽马射线照射相结合对不同癌细胞株的抗癌作用。我们分析了硝基油酸对癌症细胞株(A-549、HT-29 和 FaDu)或正常细胞株(HGF、HFF-1)的细胞死亡、细胞周期分布或 p21 和细胞周期蛋白 D1 表达的影响。计算了经 NO2OA 预处理后再进行伽马射线照射的样本在 50% 存活率下的剂量增强比(DERIC50)。NO2OA 可抑制细胞存活率并诱导细胞凋亡。这些作用具有细胞系特异性,但对癌细胞没有普遍的选择性。在测试的癌细胞系中,HT-29 细胞系对 NO2OA 处理具有更高的敏感性:诱导细胞周期停滞在 G2/M 阶段与 p21 的增加和细胞周期蛋白 D1 表达的减少有关。在辐照前用 NO2OA 预处理 HT-29 细胞,可显著提高 DERIC50,显示出放射增敏作用。总之,N2OA 具有联合化放疗的潜力。我们的研究结果鼓励人们开发具有更好特性的新型 NFAs,用于癌症化放疗。
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引用次数: 0
A structural biology view on the enzymes involved in eukaryotic mRNA turnover. 真核生物mRNA转换酶的结构生物学观点。
IF 3.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-15 Print Date: 2023-10-26 DOI: 10.1515/hsz-2023-0182
Christina Krempl, Daniela Lazzaretti, Remco Sprangers

The cellular environment contains numerous ribonucleases that are dedicated to process mRNA transcripts that have been targeted for degradation. Here, we review the three dimensional structures of the ribonuclease complexes (Pan2-Pan3, Ccr4-Not, Xrn1, exosome) and the mRNA decapping enzymes (Dcp2, DcpS) that are involved in mRNA turnover. Structures of major parts of these proteins have been experimentally determined. These enzymes and factors do not act in isolation, but are embedded in interaction networks which regulate enzyme activity and ensure that the appropriate substrates are recruited. The structural details of the higher order complexes that form can, in part, be accurately deduced from known structural data of sub-complexes. Interestingly, many of the ribonuclease and decapping enzymes have been observed in structurally different conformations. Together with experimental data, this highlights that structural changes are often important for enzyme function. We conclude that the known structural data of mRNA decay factors provide important functional insights, but that static structural data needs to be complemented with information regarding protein motions to complete the picture of how transcripts are turned over. In addition, we highlight multiple aspects that influence mRNA turnover rates, but that have not been structurally characterized so far.

细胞环境包含许多核糖核酸酶,它们专门处理被靶向降解的mRNA转录物。在此,我们综述了参与信使核糖核酸转换的核糖核酸酶复合物(Pan2-Pan3,Ccr4-Not,Xrn1,外泌体)和信使核糖核酸去帽酶(Dcp2,DcpS)的三维结构。这些蛋白质的主要部分的结构已经通过实验确定。这些酶和因子不是孤立作用的,而是嵌入相互作用网络中,调节酶活性并确保招募合适的底物。形成的高阶配合物的结构细节可以部分地从亚配合物的已知结构数据中准确推导出来。有趣的是,已经观察到许多核糖核酸酶和去帽酶在结构上不同的构象。结合实验数据,这突出表明结构变化通常对酶功能很重要。我们得出的结论是,信使核糖核酸衰变因子的已知结构数据提供了重要的功能见解,但静态结构数据需要补充有关蛋白质运动的信息,以完成转录物如何翻转的画面。此外,我们强调了影响信使核糖核酸转换率的多个方面,但迄今为止尚未对其进行结构表征。
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引用次数: 0
The archaeal Lsm protein from Pyrococcus furiosus binds co-transcriptionally to poly(U)-rich target RNAs. 来自发热热球菌的古生菌Lsm蛋白通过共转录与多U富靶rna结合。
IF 3.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-15 Print Date: 2023-10-26 DOI: 10.1515/hsz-2023-0215
Robert Reichelt, Tamara Rothmeier, Felix Grünberger, Sarah Willkomm, Astrid Bruckmann, Winfried Hausner, Dina Grohmann

Posttranscriptional processes in Bacteria include the association of small regulatory RNAs (sRNA) with a target mRNA. The sRNA/mRNA annealing process is often mediated by an RNA chaperone called Hfq. The functional role of bacterial and eukaryotic Lsm proteins is partially understood, whereas knowledge about archaeal Lsm proteins is scarce. Here, we used the genetically tractable archaeal hyperthermophile Pyrococcus furiosus to identify the protein interaction partners of the archaeal Sm-like proteins (PfuSmAP1) using mass spectrometry and performed a transcriptome-wide binding site analysis of PfuSmAP1. Most of the protein interaction partners we found are part of the RNA homoeostasis network in Archaea including ribosomal proteins, the exosome, RNA-modifying enzymes, but also RNA polymerase subunits, and transcription factors. We show that PfuSmAP1 preferentially binds messenger RNAs and antisense RNAs recognizing a gapped poly(U) sequence with high affinity. Furthermore, we found that SmAP1 co-transcriptionally associates with target RNAs. Our study reveals that in contrast to bacterial Hfq, PfuSmAP1 does not affect the transcriptional activity or the pausing behaviour of archaeal RNA polymerases. We propose that PfuSmAP1 recruits antisense RNAs to target mRNAs and thereby executes its putative regulatory function on the posttranscriptional level.

细菌的转录后过程包括小的调节RNA(sRNA)与靶mRNA的结合。sRNA/mRNA退火过程通常由一种名为Hfq的RNA伴侣介导。细菌和真核Lsm蛋白的功能作用已被部分了解,而对古菌Lsm蛋白知之甚少。在这里,我们使用基因可处理的古菌超嗜热Pyrocococcus furiosus,使用质谱法鉴定古菌Sm样蛋白(PfuSmAP1)的蛋白质相互作用伙伴,并对PfuSmAP1进行转录组全结合位点分析。我们发现的大多数蛋白质相互作用伙伴是古菌RNA同源性网络的一部分,包括核糖体蛋白质、外泌体、RNA修饰酶,还有RNA聚合酶亚基和转录因子。我们发现PfuSmAP1优先结合信使RNA和反义RNA,以高亲和力识别带间隙的聚(U)序列。此外,我们发现SmAP1与靶RNA共转录相关。我们的研究表明,与细菌Hfq相比,PfuSmAP1不影响古菌RNA聚合酶的转录活性或暂停行为。我们提出PfuSmAP1招募反义RNA靶向mRNA,从而在转录后水平上执行其假定的调节功能。
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引用次数: 0
The promise of genetic screens in human in vitro brain models. 体外人脑模型基因筛选的前景。
IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-12 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0174
Julianne Beirute-Herrera, Beatriz López-Amo Calvo, Frank Edenhofer, Christopher Esk

Advances of in vitro culture models have allowed unprecedented insights into human neurobiology. At the same time genetic screening has matured into a robust and accessible experimental strategy allowing for the simultaneous study of many genes in parallel. The combination of both technologies is a newly emerging tool for neuroscientists, opening the door to identifying causal cell- and tissue-specific developmental and disease mechanisms. However, with complex experimental genetic screening set-ups new challenges in data interpretation and experimental scope arise that require a deep understanding of the benefits and challenges of individual approaches. In this review, we summarize the literature that applies genetic screening to in vitro brain models, compare experimental strengths and weaknesses and point towards future directions of these promising approaches.

体外培养模型的进步使人们对人类神经生物学有了前所未有的了解。与此同时,基因筛选已经成熟为一个强大的和可访问的实验策略,允许同时研究许多基因并行。这两种技术的结合对神经科学家来说是一种新兴的工具,为识别细胞和组织特异性的因果发育和疾病机制打开了大门。然而,随着复杂的实验遗传筛选设置,在数据解释和实验范围方面出现了新的挑战,需要深入了解个人方法的好处和挑战。在本文中,我们总结了将遗传筛查应用于体外脑模型的文献,比较了实验的优缺点,并指出了这些有前途的方法的未来方向。
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引用次数: 0
N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4. N6-甲基腺苷诱导的 METTL1 通过 CDK4 促进肿瘤增殖。
IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-12 Print Date: 2024-03-25 DOI: 10.1515/hsz-2023-0260
Chunyan Zhang, Yuanbo Cui

N6-methyladenosine (m6A) and N7-methylguanosine (m7G) modification of RNA represent two major intracellular post-transcriptional regulation modes of gene expression. However, the crosstalk of these two epigenetic modifications in tumorigenesis remain poorly understood. Here, we show that m6A methyltransferase METTL3-mediated METTL1 promotes cell proliferation of head and neck squamous cell carcinoma (HNSC) through m7G modification of the cell-cycle regulator CDK4. By mining the database GEPIA, METTL1 was shown to be up-regulated in a broad spectrum of human cancers and correlated with patient clinical outcomes, particularly in HNSC. Mechanistically, METTL3 methylates METTL1 mRNA and mediates its elevation in HNSC via m6A. Functionally, over-expression of METTL1 enhances HNSC cell growth and facilitates cell-cycle progress, while METTL1 knockdown represses these biological behaviors. Moreover, METTL1 physically binds to CDK4 transcript and regulates its m7G modification level to stabilize CDK4. Importantly, the inhibitory effects of METTL1 knockdown on the proliferation of HNSC, esophageal cancer (ESCA), stomach adenocarcinoma (STAD), and colon adenocarcinoma (COAD) were significantly mitigated by over-expression of CDK4. Taken together, this study expands the understanding of epigenetic mechanisms involved in tumorigenesis and identifies the METTL1/CDK4 axis as a potential therapeutic target for digestive system tumors.

RNA的N6-甲基腺苷(m6A)和N7-甲基鸟苷(m7G)修饰是细胞内基因表达的两种主要转录后调控模式。然而,人们对这两种表观遗传修饰在肿瘤发生中的相互影响仍知之甚少。在这里,我们发现m6A甲基转移酶METTL3介导的METTL1通过m7G修饰细胞周期调节因子CDK4促进头颈部鳞状细胞癌(HNSC)的细胞增殖。通过挖掘 GEPIA 数据库,METTL1 被证明在多种人类癌症中上调,并与患者的临床预后相关,尤其是在 HNSC 中。从机理上讲,METTL3 甲基化 METTL1 mRNA,并通过 m6A 介导其在 HNSC 中的升高。在功能上,过度表达METTL1会增强HNSC细胞的生长并促进细胞周期的进展,而敲除METTL1则会抑制这些生物学行为。此外,METTL1与CDK4转录本物理结合,并调节其m7G修饰水平以稳定CDK4。重要的是,METTL1敲除对HNSC、食管癌(ESCA)、胃腺癌(STAD)和结肠腺癌(COAD)增殖的抑制作用因CDK4的过度表达而显著减轻。综上所述,这项研究拓展了人们对肿瘤发生过程中表观遗传学机制的认识,并将 METTL1/CDK4 轴确定为消化系统肿瘤的潜在治疗靶点。
{"title":"N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4.","authors":"Chunyan Zhang, Yuanbo Cui","doi":"10.1515/hsz-2023-0260","DOIUrl":"10.1515/hsz-2023-0260","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) and N7-methylguanosine (m7G) modification of RNA represent two major intracellular post-transcriptional regulation modes of gene expression. However, the crosstalk of these two epigenetic modifications in tumorigenesis remain poorly understood. Here, we show that m6A methyltransferase METTL3-mediated METTL1 promotes cell proliferation of head and neck squamous cell carcinoma (HNSC) through m7G modification of the cell-cycle regulator CDK4. By mining the database GEPIA, METTL1 was shown to be up-regulated in a broad spectrum of human cancers and correlated with patient clinical outcomes, particularly in HNSC. Mechanistically, METTL3 methylates METTL1 mRNA and mediates its elevation in HNSC via m6A. Functionally, over-expression of METTL1 enhances HNSC cell growth and facilitates cell-cycle progress, while METTL1 knockdown represses these biological behaviors. Moreover, METTL1 physically binds to CDK4 transcript and regulates its m7G modification level to stabilize CDK4. Importantly, the inhibitory effects of METTL1 knockdown on the proliferation of HNSC, esophageal cancer (ESCA), stomach adenocarcinoma (STAD), and colon adenocarcinoma (COAD) were significantly mitigated by over-expression of CDK4. Taken together, this study expands the understanding of epigenetic mechanisms involved in tumorigenesis and identifies the METTL1/CDK4 axis as a potential therapeutic target for digestive system tumors.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"217-228"},"PeriodicalIF":2.9,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microtubules as a signal hub for axon growth in response to mechanical force. 微管作为轴突生长响应机械力的信号中枢。
IF 3.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-08 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0173
Alessandro Falconieri, Allegra Coppini, Vittoria Raffa

Microtubules are highly polar structures and are characterized by high anisotropy and stiffness. In neurons, they play a key role in the directional transport of vesicles and organelles. In the neuronal projections called axons, they form parallel bundles, mostly oriented with the plus-end towards the axonal termination. Their physico-chemical properties have recently attracted attention as a potential candidate in sensing, processing and transducing physical signals generated by mechanical forces. Here, we discuss the main evidence supporting the role of microtubules as a signal hub for axon growth in response to a traction force. Applying a tension to the axon appears to stabilize the microtubules, which, in turn, coordinate a modulation of axonal transport, local translation and their cross-talk. We speculate on the possible mechanisms modulating microtubule dynamics under tension, based on evidence collected in neuronal and non-neuronal cell types. However, the fundamental question of the causal relationship between these mechanisms is still elusive because the mechano-sensitive element in this chain has not yet been identified.

微管是高极性结构,具有高各向异性和刚度的特点。在神经元中,它们在囊泡和细胞器的定向运输中起关键作用。在被称为轴突的神经元突起中,它们形成平行束,大多数正端朝向轴突末端。它们的物理化学性质最近引起了人们的关注,作为机械力产生的物理信号的传感、处理和转导的潜在候选者。在这里,我们讨论了支持微管作为响应牵引力轴突生长的信号中枢作用的主要证据。对轴突施加张力似乎可以稳定微管,从而协调轴突运输、局部翻译及其串扰的调制。基于在神经元和非神经元细胞类型中收集的证据,我们推测张力下调节微管动力学的可能机制。然而,这些机制之间的因果关系的基本问题仍然是难以捉摸的,因为这条链中的机械敏感元件尚未被确定。
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引用次数: 0
The Zika virus infection remodels the expression of the synaptotagmin-9 secretory protein. 寨卡病毒感染重塑了突触标记蛋白-9分泌蛋白的表达。
IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-08 Print Date: 2024-03-25 DOI: 10.1515/hsz-2023-0165
Santiago Leiva, Alejo Cantoia, Cintia Fabbri, Marina Bugnon Valdano, Victoria Luppo, María Alejandra Morales, Germán Rosano, Daniela Gardiol

The exact mechanisms involved in flaviviruses virions' release and the specific secretion of viral proteins, such as the Non Structural protein-1 (NS1), are still unclear. While these processes might involve vesicular transport to the cell membrane, NS1 from some flaviviruses was shown to participate in viral assembly and release. Here, we assessed the effect of the Zika virus (ZIKV) NS1 expression on the cellular proteome to identify trafficking-related targets that may be altered in the presence of the viral protein. We detected an increase in the synaptotagmin-9 (SYT9) secretory protein, which participates in the intracellular transport of protein-laden vesicles. We confirmed the effect of NS1 on SYT9 levels by transfection models while also detecting a significant subcellular redistribution of SYT9. We found that ZIKV prM-Env proteins, required for the viral particle release, also increased SYT9 levels and changed its localization. Finally, we demonstrated that ZIKV cellular infection raises SYT9 levels and promotes changes in its subcellular localization, together with a co-distribution with both Env and NS1. Altogether, the data suggest SYT9's implication in the vesicular transport of viral proteins or virions during ZIKV infection, showing for the first time the association of synaptotagmins with the flavivirus' life cycle.

黄病毒病毒释放和特定分泌病毒蛋白(如非结构蛋白-1(NS1))的确切机制仍不清楚。虽然这些过程可能涉及到向细胞膜的囊泡运输,但一些黄病毒的 NS1 被证明参与了病毒的组装和释放。在此,我们评估了寨卡病毒(ZIKV)NS1的表达对细胞蛋白质组的影响,以确定病毒蛋白存在时可能会改变的与转运相关的靶标。我们检测到突触标记蛋白-9 (SYT9)分泌蛋白的增加,该蛋白参与细胞内蛋白载囊的转运。我们通过转染模型证实了 NS1 对 SYT9 水平的影响,同时还检测到了 SYT9 的显著亚细胞再分布。我们发现,病毒粒子释放所需的 ZIKV prM-Env 蛋白也会增加 SYT9 的水平并改变其定位。最后,我们证明 ZIKV 细胞感染会提高 SYT9 的水平并促进其亚细胞定位的变化,同时与 Env 和 NS1 共同分布。总之,这些数据表明 SYT9 在 ZIKV 感染过程中参与了病毒蛋白或病毒的囊泡运输,首次显示了突触素与黄病毒生命周期的联系。
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引用次数: 0
Cytosolic RGG RNA-binding proteins are temperature sensitive flowering time regulators in Arabidopsis. 拟南芥细胞质RGG rna结合蛋白是温度敏感的开花时间调节因子。
IF 3.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-08 Print Date: 2023-10-26 DOI: 10.1515/hsz-2023-0171
Andrea Bleckmann, Nicole Spitzlberger, Philipp Denninger, Hans F Ehrnsberger, Lele Wang, Astrid Bruckmann, Stefan Reich, Philipp Holzinger, Jan Medenbach, Klaus D Grasser, Thomas Dresselhaus

mRNA translation is tightly regulated by various classes of RNA-binding proteins (RBPs) during development and in response to changing environmental conditions. In this study, we characterize the arginine-glycine-glycine (RGG) motif containing RBP family of Arabidopsis thaliana representing homologues of the multifunctional translation regulators and ribosomal preservation factors Stm1 from yeast (ScStm1) and human SERBP1 (HsSERBP1). The Arabidopsis genome encodes three RGG proteins named AtRGGA, AtRGGB and AtRGGC. While AtRGGA is ubiquitously expressed, AtRGGB and AtRGGC are enriched in dividing cells. All AtRGGs localize almost exclusively to the cytoplasm and bind with high affinity to ssRNA, while being capable to interact with most nucleic acids, except dsRNA. A protein-interactome study shows that AtRGGs interact with ribosomal proteins and proteins involved in RNA processing and transport. In contrast to ScStm1, AtRGGs are enriched in ribosome-free fractions in polysome profiles, suggesting additional plant-specific functions. Mutant studies show that AtRGG proteins differentially regulate flowering time, with a distinct and complex temperature dependency for each AtRGG protein. In conclusion, we suggest that AtRGGs function in fine-tuning translation efficiency to control flowering time and potentially other developmental processes in response to environmental changes.

mRNA翻译在发育过程中受到各类RNA结合蛋白(RBPs)的严格调控,并对不断变化的环境条件作出反应。在本研究中,我们对拟南芥的含有精氨酸-甘氨酸(RGG)基序的RBP家族进行了表征,该家族代表了来自酵母(ScStm1)和人SERBP1(HsSERBP1)的多功能翻译调节因子和核糖体保存因子Stm1的同源物。拟南芥基因组编码三种RGG蛋白,分别命名为AtRGGA、AtRGGB和AtRGGC。当AtRGGA普遍表达时,AtRGGB和AtRGGC在分裂细胞中富集。所有的AtRGG几乎完全定位于细胞质,并与ssRNA高亲和力结合,同时能够与除dsRNA外的大多数核酸相互作用。一项蛋白质相互作用组研究表明,AtRGG与核糖体蛋白质和参与RNA加工和转运的蛋白质相互作用。与ScStm1相比,AtRGG在多糖体图谱中富含无核糖体的部分,这表明它具有额外的植物特异性功能。突变体研究表明,AtRGG蛋白对开花时间有不同的调节作用,每种AtRGG蛋白质都具有独特而复杂的温度依赖性。总之,我们认为AtRGGs的作用是微调翻译效率,以控制开花时间和潜在的其他发育过程,以应对环境变化。
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引用次数: 0
Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation. 突触前末端CaV2.1剪接异构体的纳米级组织:对突触小泡释放和突触促进的意义。
IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-09-04 Print Date: 2023-09-26 DOI: 10.1515/hsz-2023-0235
Lorenzo A Cingolani, Agnes Thalhammer, Fanny Jaudon, Jessica Muià, Gabriele Baj

The distance between CaV2.1 voltage-gated Ca2+ channels and the Ca2+ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of CaV2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two CaV2.1 splice isoforms (CaV2.1[EFa] and CaV2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that CaV2.1[EFa] is more tightly co-localized with presynaptic markers than CaV2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of CaV2.1 channels.

CaV2.1电压门控Ca2+通道和负责突触前末端囊泡释放的Ca2+传感器之间的距离对于确定突触强度至关重要。然而,导致CaV2.1在某些突触或发育期出现松散耦合配置,而在其他突触或发育时期出现紧密耦合配置的分子机制仍然未知。在这里,我们通过超分辨率结构照明显微镜检查了两种CaV2.1剪接异构体(CaV2.1[EFa]和CaV2.1[EFb])在突触前末端的纳米级组织。我们发现,与CaV2.1[EFb]相比,CaV2.1[EFa]与突触前标记物更紧密地共定位,这表明选择性剪接在CaV2.1通道的突触组织中起着至关重要的作用。
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引用次数: 0
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