The translatome of neuronal cell bodies, dendrites, and axons.
The translatome of neuronal cell bodies, dendrites, and axons.
复制标题
DOI：
10.1073/pnas.2113929118
复制
发表时间：
2021-10-26
影响因子：
11.1
通讯作者：
Schuman EM
中科院分区：
文献类型：
--
作者：
Glock C;Biever A;Tushev G;Nassim-Assir B;Kao A;Bartnik I;Tom Dieck S;Schuman EM
蛋白质是神经元突触功能的关键驱动因素。基因表达的调节对于整个生命周期中突触的形成和修饰是重要的。树突和轴突的复杂性对偏远地区的蛋白质供应提出了独特的挑战。突触附近信使RNA（mRNA）和核糖体的发现表明，局部蛋白质合成代表了这一挑战的重要解决方案。在这里，我们使用RNA测序和核糖体测序来直接确定在神经元细胞体、树突和轴突中存在和翻译过程中的mRNA群体。数以千计的转录本在细胞体和突触区域之间差异翻译，其中超过800种mRNA在树突-轴突隔室中表现出更多的翻译。为了形成突触连接和存储信息，神经元不断重塑它们的蛋白质组。树突和轴突的长度令人印象深刻，这给在远离转录源（细胞核）的位置维持突触蛋白带来了后勤挑战。在突触附近发现了成千上万的信使RNA（mRNA），这表明神经元通过在局部产生蛋白质来克服距离并获得自主性。然而，通常不知道是否、如何以及何时定位的mRNA被翻译成蛋白质。为了研究神经元亚区的翻译景观，我们从显微解剖的啮齿动物脑切片中进行了同步RNA测序（RNA-seq）和核糖体测序（Ribo-seq），以识别和量化细胞体（胞体）以及树突和轴突（神经元）中的转录组和翻译组。成千上万的转录本在体细胞和突触区域之间差异翻译，许多支架和信号分子在神经元中显示出增加的翻译水平。隔室之间的大多数翻译变化可以通过RNA丰度的差异来解释。在受特定mRNA特征（例如，非翻译区[UTR]长度、RNA结合蛋白[RBP]基序和上游开放阅读框[uORF]）。对于超过800种mRNA来说，主要的翻译来源是神经毡。我们构建了一个可搜索和交互式的数据库，用于探索mRNA转录物及其在胞体和神经元中的翻译水平[MPI Brain Research，The mRNA translation landscape in the synaptic neurology. https://public.brain.mpg.de/dashapps/localseq/. 2021年10月5日]。总体而言，我们的研究结果强调了本地翻译对维持突触蛋白水平的重大贡献，并表明现场翻译控制是控制突触强度的重要机制。
Proteins are the key drivers of neuronal synaptic function. The regulation of gene expression is important for the formation and modification of synapses throughout the lifespan. The complexity of dendrites and axons imposes unique challenges for protein supply at remote locations. The discovery of messenger RNAs (mRNAs) and ribosomes near synapses has shown that local protein synthesis represents an important solution to this challenge. Here we used RNA sequencing and ribosome sequencing to determine directly the population of mRNAs that is present and in the process of translation in neuronal cell bodies, dendrites, and axons. Thousands of transcripts were differentially translated between the cell body and synaptic regions with over 800 mRNAs exhibiting more translation in the dendritic–axonal compartment. To form synaptic connections and store information, neurons continuously remodel their proteomes. The impressive length of dendrites and axons imposes logistical challenges to maintain synaptic proteins at locations remote from the transcription source (the nucleus). The discovery of thousands of messenger RNAs (mRNAs) near synapses suggested that neurons overcome distance and gain autonomy by producing proteins locally. It is not generally known, however, if, how, and when localized mRNAs are translated into protein. To investigate the translational landscape in neuronal subregions, we performed simultaneous RNA sequencing (RNA-seq) and ribosome sequencing (Ribo-seq) from microdissected rodent brain slices to identify and quantify the transcriptome and translatome in cell bodies (somata) as well as dendrites and axons (neuropil). Thousands of transcripts were differentially translated between somatic and synaptic regions, with many scaffold and signaling molecules displaying increased translation levels in the neuropil. Most translational changes between compartments could be accounted for by differences in RNA abundance. Pervasive translational regulation was observed in both somata and neuropil influenced by specific mRNA features (e.g., untranslated region [UTR] length, RNA-binding protein [RBP] motifs, and upstream open reading frames [uORFs]). For over 800 mRNAs, the dominant source of translation was the neuropil. We constructed a searchable and interactive database for exploring mRNA transcripts and their translation levels in the somata and neuropil [MPI Brain Research, The mRNA translation landscape in the synaptic neuropil. https://public.brain.mpg.de/dashapps/localseq/. Accessed 5 October 2021]. Overall, our findings emphasize the substantial contribution of local translation to maintaining synaptic protein levels and indicate that on-site translational control is an important mechanism to control synaptic strength.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
4.8
作者：
Bal NV;Susorov D;Chesnokova E;Kasianov A;Mikhailova T;Alkalaeva E;Balaban PM;Kolosov P
通讯作者：
Kolosov P
影响因子：
4.6
作者：
Fernandes LD;Moura APS;Ciandrini L
通讯作者：
Ciandrini L
影响因子：
7.7
作者：
Alvarez-Castelao, Beatriz;Dieck, Susanne Tom;Schuman, Erin M.
通讯作者：
Schuman, Erin M.