G-四链体 RNA 结构作为神经突 mRNA 靶向的信号。
G-quadruplex RNA structure as a signal for neurite mRNA targeting.
机构信息
IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), CNRS, UMR7104, Inserm, U596, Collège de France, Strasbourg University, Illkirch-Graffenstaden 67404, France.
出版信息
EMBO Rep. 2011 Jul 1;12(7):697-704. doi: 10.1038/embor.2011.76.
Abstract
Targeting of messenger RNAs (mRNAs) in neuron processes relies on cis-acting regulatory elements, the nature of which is poorly understood. Here, we report that approximately 30% of the best-known dendritic mRNAs contain a guanine (G)-quadruplex consensus in their 3'-untranslated region. Among these mRNAs, we show by using RNA structure probing that a G-quadruplex is present in the mRNAs of two key postsynaptic proteins: PSD-95 and CaMKIIa. The G-quadruplex structure is necessary and sufficient for the potent and fast localization of mRNAs in cortical neurites and this occurs in a metabotropic glutamate receptor-responsive manner. Thus, G-quadruplex seems to be a common neurite localization signal.
摘要
靶向神经元过程中的信使 RNA（mRNA）依赖于顺式作用调节元件，但这些元件的性质尚未完全了解。在这里，我们报告说，大约 30%的最著名的树突状 mRNA 在其 3'非翻译区含有鸟嘌呤（G）四链体的共识序列。在这些 mRNA 中，我们通过使用 RNA 结构探测显示，两个关键的突触后蛋白 PSD-95 和 CaMKIIa 的 mRNA 中存在 G-四链体。G-四链体结构对于 mRNA 在皮质神经元突中的有效和快速定位是必需和充分的，这种定位方式发生在代谢型谷氨酸受体反应的方式。因此，G-四链体似乎是一种常见的神经元突定位信号。
相似文献
1
G-quadruplex RNA structure as a signal for neurite mRNA targeting.G-四链体 RNA 结构作为神经突 mRNA 靶向的信号。
EMBO Rep. 2011 Jul 1;12(7):697-704. doi: 10.1038/embor.2011.76.
2
G quadruplex RNA structures in PSD-95 mRNA: potential regulators of miR-125a seed binding site accessibility.PSD-95 mRNA中的G-四链体RNA结构：miR-125a种子结合位点可及性的潜在调节因子
RNA. 2015 Jan;21(1):48-60. doi: 10.1261/rna.046722.114. Epub 2014 Nov 18.
3
TDP-43 binds and transports G-quadruplex-containing mRNAs into neurites for local translation.TDP-43结合并将含有G-四链体的mRNA转运到神经突中进行局部翻译。
Genes Cells. 2016 May;21(5):466-81. doi: 10.1111/gtc.12352. Epub 2016 Feb 24.
4
Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome.靶向 G-四链体 DNA 作为 ATR-X 综合征的认知功能治疗方法。
Nat Med. 2018 Jun;24(6):802-813. doi: 10.1038/s41591-018-0018-6. Epub 2018 May 21.
5
2D meets 4G: G-quadruplexes in RNA secondary structure prediction.2D 遇见 4G：RNA 二级结构预测中的 G-四链体。
IEEE/ACM Trans Comput Biol Bioinform. 2013 Jul-Aug;10(4):832-44. doi: 10.1109/TCBB.2013.7.
6
FMRP - G-quadruplex mRNA - miR-125a interactions: Implications for miR-125a mediated translation regulation of PSD-95 mRNA.FMRP- G-四链体 mRNA- miR-125a 相互作用：对 miR-125a 介导的 PSD-95 mRNA 翻译调控的影响。
PLoS One. 2019 May 21;14(5):e0217275. doi: 10.1371/journal.pone.0217275. eCollection 2019.
7
Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome.在脆性X综合征小鼠模型中，代谢型谷氨酸受体依赖性的AMPA受体和突触后致密蛋白95 mRNA在突触处的翻译失调。
J Neurosci. 2007 May 16;27(20):5338-48. doi: 10.1523/JNEUROSCI.0937-07.2007.
8
Deciphering the Enigmatic Biological Functions of RNA Guanine-Quadruplex Motifs in Human Cells.解析人类细胞中 RNA 鸟嘌呤-四链体基序的神秘生物学功能。
Biochemistry. 2019 Feb 5;58(5):305-311. doi: 10.1021/acs.biochem.8b00904. Epub 2018 Oct 24.
9
Different recognition modes of G-quadruplex RNA between two ALS/FTLD-linked proteins TDP-43 and FUS.肌萎缩侧索硬化症/额颞叶痴呆相关的两种蛋白质TDP-43和FUS对G-四链体RNA的不同识别模式。
FEBS Lett. 2021 Feb;595(3):310-323. doi: 10.1002/1873-3468.14013. Epub 2020 Dec 20.
10
alpha-Isoform of calcium-calmodulin-dependent protein kinase II and postsynaptic density protein 95 differentially regulate synaptic expression of NR2A- and NR2B-containing N-methyl-d-aspartate receptors in hippocampus.钙调蛋白依赖性蛋白激酶II的α亚型和突触后致密蛋白95对海马中含NR2A和NR2B的N-甲基-D-天冬氨酸受体的突触表达有不同的调节作用。
Neuroscience. 2008 Jan 2;151(1):43-55. doi: 10.1016/j.neuroscience.2007.09.075. Epub 2007 Oct 12.
引用本文的文献
1
TDP-43 binds to RNA G-quadruplex structure and regulates mRNA stability and translation.TDP-43与RNA G-四链体结构结合并调节mRNA的稳定性和翻译。
Nucleic Acids Res. 2025 Aug 27;53(16). doi: 10.1093/nar/gkaf820.
2
Transcriptome-wide RNA accessibility mapping reveals structured RNA elements and pervasive conformational rearrangements under stress.全转录组RNA可及性图谱揭示了应激条件下的结构化RNA元件和普遍的构象重排。
bioRxiv. 2025 Jun 5:2025.06.05.658101. doi: 10.1101/2025.06.05.658101.
3
Neurological Diseases can be Regulated by Phase Separation.神经系统疾病可通过相分离来调节。
Rev Physiol Biochem Pharmacol. 2025;187:273-338. doi: 10.1007/978-3-031-68827-0_16.
4
Selective recognition of RNA G-quadruplex in vitro and in cells by L-aptamer-D-oligonucleotide conjugate.L-适配体-D-寡核苷酸共轭物在体外和细胞中对RNA G-四链体的选择性识别
Nucleic Acids Res. 2024 Dec 11;52(22):13544-13560. doi: 10.1093/nar/gkae1034.
5
Entangled World of DNA Quadruplex Folds.DNA 四链体折叠的纠缠世界。
ACS Omega. 2024 Sep 5;9(37):38696-38709. doi: 10.1021/acsomega.4c04579. eCollection 2024 Sep 17.
6
CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.CGG 重复序列在人类 FMR1 基因中调节发育神经元中的 mRNA 定位和细胞应激。
Cell Rep. 2024 Jun 25;43(6):114330. doi: 10.1016/j.celrep.2024.114330. Epub 2024 Jun 11.
7
PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells.PRMT5 介导的 FXR1 精氨酸甲基化对于癌细胞中的 RNA 结合至关重要。
Nucleic Acids Res. 2024 Jul 8;52(12):7225-7244. doi: 10.1093/nar/gkae319.
8
Signaling mechanisms underlying activity-dependent integration of adult-born neurons in the mouse olfactory bulb.活动依赖性整合成年新生神经元的信号机制在小鼠嗅球中的作用。
Genesis. 2024 Apr;62(2):e23595. doi: 10.1002/dvg.23595.
9
Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles.聚焦 G-四链体：从结构和调节到生理和病理作用。
Int J Mol Sci. 2024 Mar 9;25(6):3162. doi: 10.3390/ijms25063162.
10
The role of secondary structures in the functioning of 3' untranslated regions of mRNA: A review of functions of 3' UTRs' secondary structures and hypothetical involvement of secondary structures in cytoplasmic polyadenylation in Drosophila.二级结构在 mRNA 3'非翻译区功能中的作用：对 3'UTR 二级结构功能的综述及二级结构在果蝇细胞质多聚腺苷酸化中假设性作用的研究。
Bioessays. 2024 Mar;46(3):e2300099. doi: 10.1002/bies.202300099. Epub 2023 Dec 31.
本文引用的文献
1
Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein.脆性 X 智力低下蛋白缺失的神经元中 mRNA 运输、对接和蛋白质翻译的改变。
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15601-6. doi: 10.1073/pnas.1010564107. Epub 2010 Aug 16.
2
Subcellular mRNA localization in animal cells and why it matters.动物细胞中的亚细胞mRNA定位及其重要性。
Science. 2009 Nov 27;326(5957):1212-6. doi: 10.1126/science.1176488.
3
Kinesin superfamily motor proteins and intracellular transport.驱动蛋白超家族运动蛋白与细胞内运输
Nat Rev Mol Cell Biol. 2009 Oct;10(10):682-96. doi: 10.1038/nrm2774.
4
To localize or not to localize: mRNA fate is in 3'UTR ends.定位与否：mRNA的命运取决于3'非翻译区末端。
Trends Cell Biol. 2009 Sep;19(9):465-74. doi: 10.1016/j.tcb.2009.06.001. Epub 2009 Aug 26.
5
G-quadruplex structures: in vivo evidence and function.G-四链体结构：体内证据与功能
Trends Cell Biol. 2009 Aug;19(8):414-22. doi: 10.1016/j.tcb.2009.05.002. Epub 2009 Jul 7.
6
RNA localization and polarity: from A(PC) to Z(BP).RNA定位与极性：从A（PC）到Z（BP）
Trends Cell Biol. 2009 Apr;19(4):156-64. doi: 10.1016/j.tcb.2009.02.001. Epub 2009 Feb 27.
7
mRNA localization: gene expression in the spatial dimension.mRNA定位：空间维度上的基因表达。
Cell. 2009 Feb 20;136(4):719-30. doi: 10.1016/j.cell.2009.01.044.
8
Translational control of long-lasting synaptic plasticity and memory.持久突触可塑性和记忆的翻译调控
Neuron. 2009 Jan 15;61(1):10-26. doi: 10.1016/j.neuron.2008.10.055.
9
Dendrites of mammalian neurons contain specialized P-body-like structures that respond to neuronal activation.哺乳动物神经元的树突含有对神经元激活作出反应的特殊的类P小体结构。
J Neurosci. 2008 Dec 17;28(51):13793-804. doi: 10.1523/JNEUROSCI.4155-08.2008.
10
Translational control of localized mRNAs: restricting protein synthesis in space and time.局部化mRNA的翻译调控：在空间和时间上限制蛋白质合成
Nat Rev Mol Cell Biol. 2008 Dec;9(12):971-80. doi: 10.1038/nrm2548.
Zotero 插件