Role of ER-membrane contacts in biogenesis of RNA-containing EVs
内质网膜接触在含 RNA EV 生物发生中的作用
基本信息
- 批准号:10544789
- 负责人:
- 金额:$ 34.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-22 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAutomobile DrivingBehaviorBindingBiochemicalBiogenesisBiological ModelsCell membraneCellsCellular MembraneCeramidesCetuximabCholesterolCodeCollecting CellCommunicationComplexDataEndoplasmic ReticulumEndosomesEngineeringEpidermal Growth Factor ReceptorEventFractionationGene ExpressionHealthHumanIn VitroKRAS2 geneLarge Intestine CarcinomaLinkLipidsMalignant Epithelial CellMediatingMembraneMessenger RNAMethodsMicroRNAsOrganellesPhenotypePoly(A)+ RNAPolyribosomesProteinsRNARNA BindingRNA TransportRNA-Binding ProteinsRNA-Induced Silencing ComplexResearchResistanceRibosomal ProteinsRibosomesRoleRough endoplasmic reticulumRouteSignal TransductionSiteSmall Nucleolar RNATestingTissuesTransfer RNAUbiquitinationUntranslated RNAVesicleendosome membraneexosomeextracellularextracellular vesiclesgene functionin vivoknock-downlate endosomelipid transportmRNA Translationmicrovesiclesnoveloverexpressionpalmitoylationprotein complexreceptorrelease of sequestered calcium ion into cytoplasmsegregationsmall hairpin RNAtraittranscriptome sequencingtumortumor growthtumor microenvironmenttumorigenesisubiquitin ligase
项目摘要
Project 1 Summary:
Extracellular vesicles (EVs) carry a variety of RNAs, including both coding and noncoding RNAs. These
RNAs have the potential to influence cell and tissue phenotypes. Indeed for miRNAs there are now many
examples of EV-carried miRNA controlling gene expression and function in recipient cells. RNA-Seq analyses
have demonstrated specific enrichment of some RNAs in EVs, compared to the cellular content. However, very
little is known about the specific mechanisms by which RNA is transported into EVs.
The current paradigm, based on several studies, is that RNA-binding proteins (RBPs) are responsible
for the selective and specific inclusion of RNAs in EVs. However, how those RBPs connect to cellular
membranes to be incorporated into shed microvesicles (MVs) or late endosome-derived exosomes is
unknown. A notable finding is that many RBPs identified in EVs are typically associated with the endoplasmic
reticulum (ER) in cells, suggesting a potential role for the ER in transfer of those moieties to other organelles.
Furthermore, the RNA-induced silencing complex is assembled on mRNA-ribosome complexes associated
with the ER (rough ER), suggesting a route for miRNA-RBP association with the ER and subsequently other
membranes. Based on these findings and our preliminary data, we hypothesize that ER-plasma membrane
(PM) and ER-multivesicular endosome (MVE) membrane contact sites (MCS) are critical for transfer of RNAs
and RBPs into shed microvesicles and exosomes. We further hypothesize that signaling and lipid transfer
events taking place at these contacts further regulate RNA transport into vesicles. We will test these
hypotheses and determine the impact of MCS on transfer of RNAs to recipient cells and CRC tumor growth
and cetuximab resistance.
项目1摘要:
细胞外囊泡(EV)携带多种RNA,包括编码和非编码RNA。这些
RNA具有影响细胞和组织表型的潜力。事实上,对于miRNAs,
EV携带的miRNA在受体细胞中控制基因表达和功能的例子。RNA-Seq分析
已经证明了与细胞内容物相比,EV中某些RNA的特异性富集。可是
关于RNA被转运到EV中的具体机制知之甚少。
基于几项研究,目前的范式是RNA结合蛋白(RBP)负责
在EV中选择性和特异性地包含RNA。然而,这些RBP如何连接到蜂窝网络
将膜掺入脱落微泡(MV)或晚期内体衍生的外泌体中的方法是
未知一个值得注意的发现是,在EV中鉴定的许多RBP通常与内质网相关,
细胞中的内质网(ER),这表明ER在将这些部分转移到其他细胞器中的潜在作用。
此外,RNA诱导的沉默复合物组装在mRNA-核糖体复合物上,
与ER(粗糙ER),这表明了miRNA-RBP与ER以及随后的其他
膜。基于这些发现和我们的初步数据,我们假设ER-质膜
(PM)ER-多泡内体(MVE)膜接触位点(MCS)是RNA转移的关键
和RBP转化为脱落的微泡和外泌体。我们进一步假设信号传导和脂质转移
在这些接触处发生的事件进一步调节RNA转运到囊泡中。我们将测试这些
并确定MCS对RNA转移至受体细胞和CRC肿瘤生长的影响
和西妥昔单抗抗性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alissa M Weaver其他文献
Alissa M Weaver的其他文献
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{{ truncateString('Alissa M Weaver', 18)}}的其他基金
exRNA in colorectal carcinoma: biogenesis and function
结直肠癌中的 exRNA:生物发生和功能
- 批准号:
10544788 - 财政年份:2020
- 资助金额:
$ 34.26万 - 项目类别:
Phenotype Interactions in SCLC Development and Detection
SCLC 发展和检测中的表型相互作用
- 批准号:
10472576 - 财政年份:2018
- 资助金额:
$ 34.26万 - 项目类别:
Phenotype Interactions and Dynamics in SCLC Tumors
SCLC 肿瘤的表型相互作用和动态
- 批准号:
10375423 - 财政年份:2018
- 资助金额:
$ 34.26万 - 项目类别:
Phenotype Interactions in SCLC Development and Detection
SCLC 发展和检测中的表型相互作用
- 批准号:
10246932 - 财政年份:2018
- 资助金额:
$ 34.26万 - 项目类别:
Phenotype Interactions in SCLC Development and Detection
SCLC 发展和检测中的表型相互作用
- 批准号:
9788304 - 财政年份:2018
- 资助金额:
$ 34.26万 - 项目类别:
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