Identification of 3' UTR motifs required for mRNA localization to myelin sheaths in vivo.
Identification of 3' UTR motifs required for mRNA localization to myelin sheaths in vivo.
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DOI：
10.1371/journal.pbio.3001053
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发表时间：
2021-01
期刊：
影响因子：
9.8
通讯作者：
Appel B
中科院分区：
文献类型：
--
作者：
Yergert KM;Doll CA;O'Rouke R;Hines JH;Appel B
髓鞘是由少突胶质细胞产生的一种特殊的膜，其隔离并支持轴突。少突胶质细胞延伸出许多细胞突起，作为质膜的突起，同时将多层髓鞘膜包裹在靶轴突周围。值得注意的是，髓鞘起源于同一少突胶质细胞的大小是可变的，这表明局部机制调节髓鞘生长。纯化的髓鞘含有核糖体和数百种mRNA，支持mRNA定位和局部蛋白质合成调节鞘生长和成熟的模型。然而，mRNA选择性富集在髓鞘中的机制尚不清楚。为了研究mRNA是如何靶向髓鞘的，我们测试了这样一个假设，即转录本是通过3′非翻译区（3′ UTR）中的共有序列被选择用于髓鞘富集。利用活体斑马鱼幼鱼中mRNA的可视化方法，我们鉴定了足以将mRNA定位于鞘并在新生膜生长区附近富集的候选3′ UTR。我们从3个富含髓鞘的转录物中鉴定了3′ UTR中常见的基序，并确定这些基序是mRNA转运到髓鞘所必需的，并且以依赖于上下文的方式足够。最后，我们发现，1基序是高度富集的髓鞘转录组，这表明该序列是一个全球性的调节mRNA定位在髓鞘形成的发展。使用方法可视化mRNA在活的斑马鱼幼虫，本研究确定候选基序3'UTR，足以定位mRNA的髓鞘，这样的基序是高度富集在髓鞘转录组，这表明该序列是一个全球性的监管机构的mRNA定位在髓鞘发育。
Myelin is a specialized membrane produced by oligodendrocytes that insulates and supports axons. Oligodendrocytes extend numerous cellular processes, as projections of the plasma membrane, and simultaneously wrap multiple layers of myelin membrane around target axons. Notably, myelin sheaths originating from the same oligodendrocyte are variable in size, suggesting local mechanisms regulate myelin sheath growth. Purified myelin contains ribosomes and hundreds of mRNAs, supporting a model that mRNA localization and local protein synthesis regulate sheath growth and maturation. However, the mechanisms by which mRNAs are selectively enriched in myelin sheaths are unclear. To investigate how mRNAs are targeted to myelin sheaths, we tested the hypothesis that transcripts are selected for myelin enrichment through consensus sequences in the 3′ untranslated region (3′ UTR). Using methods to visualize mRNA in living zebrafish larvae, we identified candidate 3′ UTRs that were sufficient to localize mRNA to sheaths and enriched near growth zones of nascent membrane. We bioinformatically identified motifs common in 3′ UTRs from 3 myelin-enriched transcripts and determined that these motifs are required and sufficient in a context-dependent manner for mRNA transport to myelin sheaths. Finally, we show that 1 motif is highly enriched in the myelin transcriptome, suggesting that this sequence is a global regulator of mRNA localization during developmental myelination. Using methods to visualize mRNA in living zebrafish larvae, this study identifies candidate motifs 3’ UTRs that were sufficient to localize mRNA to myelin sheaths; one such motif is highly enriched in the myelin transcriptome, suggesting that this sequence is a global regulator of mRNA localization during developmental myelination.
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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：
5.3
作者：
Buckanovich, RJ;Darnell, RB
通讯作者：
Darnell, RB
影响因子：
5.3
作者：
Banko, JL;Poulin, F;Klann, E
通讯作者：
Klann, E
影响因子：
3.3
作者：
de Vries, H;Schrage, C;Hoekstra, D
通讯作者：
Hoekstra, D
影响因子：
64.8
作者：
Hachet, O;Ephrussi, A
通讯作者：
Ephrussi, A