Upstream regulation of microRNA-9 through a complex cellular machinery during neurogenesis

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2024-11-14 DOI:10.1016/j.brainres.2024.149328

Diji Kuriakose , Hong-mei Zhu , Yi-ling Zhao , Fuad A. Iraqi , Grant Morahan , Zhi-cheng Xiao

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Abstract

Summary

While microRNAs (miRs) like miR-9 are crucial for neurogenesis and neuronal differentiation, their regulatory mechanisms are not well understood. miR-9 is highly expressed in the brain and plays a significant role in neurogenesis. Using the Collaborative Cross resource, we identified significant quantitative trait loci (QTL) through genetic analyses. We then characterized over 130 candidate genes within these QTL regions using RNA interference, qPCR, and neuronal differentiation assays, narrowing them down to 13 promising candidates. Among these, Panx2, Polr1c, and Mgea5 were found to colocalize in the neurogenic niches of the SVZ and DG regions, as shown by immunofluorescence. Further ChIP-seq and Co-IP analyses revealed their interaction and binding to the miR-9 locus, forming a DNA-protein regulatory complex we termed ’miRSome-9.’ A 3C/ChIP-loop assay confirmed the chromatin organization of miRSome-9 at the miR-9 locus, shedding light on the upstream mechanisms regulating miR-9 expression during neurogenesis.

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在神经发生过程中，通过复杂的细胞机制对 microRNA-9 进行上游调控。

虽然miR-9等微RNA（miRs）对神经发生和神经元分化至关重要，但它们的调控机制并不十分清楚。miR-9在大脑中高度表达，在神经发生中发挥着重要作用。利用协作交叉资源，我们通过遗传分析确定了重要的数量性状位点（QTL）。然后，我们利用 RNA 干扰、qPCR 和神经元分化实验对这些 QTL 区域内的 130 多个候选基因进行了表征，最终将候选基因缩小到 13 个。免疫荧光显示，其中Panx2、Polr1c和Mgea5在SVZ和DG区域的神经源龛中共定位。进一步的 ChIP-seq 和 Co-IP 分析揭示了它们与 miR-9 基因座的相互作用和结合，形成了我们称之为 "miRSome-9 "的 DNA 蛋白调控复合物。3C/ChIP环分析证实了miRSome-9在miR-9基因座上的染色质组织，揭示了神经发生过程中调控miR-9表达的上游机制。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.