Whole-transcriptome microarray analysis reveals regulation of Rab4 by RBM5 in neurons.
Whole-transcriptome microarray analysis reveals regulation of Rab4 by RBM5 in neurons.
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DOI：
10.1016/j.neuroscience.2017.08.014
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发表时间：
2017-10-11
期刊：
影响因子：
3.3
通讯作者：
Kochanek PM
中科院分区：
文献类型：
--
作者：
Jackson TC;Kotermanski SE;Kochanek PM
RNA结合基序5（RBM 5）是调节癌细胞中基因转录和mRNA剪接的核蛋白。脑是体内RBM 5表达最高的器官之一，但其mRNA靶标或在CNS中的功能尚未阐明。在这里，我们在原代大鼠皮层神经元中敲低（KO）RBM 5，并通过基因微阵列与用慢病毒转导以递送对照（非靶向）shRNA的神经元分析总RNA提取物。与对照组相比，RBM 5 KO神经元中Sec 23 A（参与ER-高尔基体转运）和小GTdR Rab 4a（参与内吞作用/蛋白质转运）的mRNA水平增加。在蛋白质水平，RBM 5 KO提取物中仅Rab 4a显著增加。此外，KO神经元中Rab 4a水平升高与寡聚5-羟色胺转运体（SERT）的膜水平降低相关。最后，RBM 5 KO与膜衍生的单体SERT的摄取增加相关。Rab 4a参与细胞内吞和蛋白质运输的调节。在CNS中，它调节多种神经生物学功能，包括（但不限于）参与神经传递的跨膜蛋白（例如SERT）的运输、维持树突棘大小、促进轴突生长和调节认知。我们的研究结果表明，RBM 5调节Rab 4a在大鼠神经元。
RNA binding motif 5 (RBM5) is a nuclear protein that modulates gene transcription and mRNA splicing in cancer cells. The brain is among the highest RBM5 expressing organ in the body but its mRNA target(s) or functions in the CNS have not been elucidated. Here we knocked down (KO) RBM5 in primary rat cortical neurons and analyzed total RNA extracts by gene microarray vs. neurons transduced with lentivirus to deliver control (non-targeting) shRNA. The mRNA levels of Sec23A (involved in ER-Golgi transport) and the small GTPase Rab4a (involved in endocytosis/protein trafficking) were increased in RBM5 KO neurons relative to controls. At the protein level, only Rab4a was significantly increased in RBM5 KO extracts. Also, elevated Rab4a levels in KO neurons were associated with decreased membrane levels of oligomeric serotonin transporters (SERT). Finally, RBM5 KO was associated with increased uptake of membrane-derived monomeric SERT. Significance: Rab4a is involved in the regulation of endocytosis and protein trafficking in cells. In the CNS it regulates diverse neurobiological functions including (but not limited to) trafficking of transmembrane proteins involved in neurotransmission (e.g. SERT), maintaining dendritic spine size, promoting axonal growth, and modulates cognition. Our findings suggest that RBM5 regulates Rab4a in rat neurons.
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