LncRNA 3222401L13Rik Is Upregulated in Aging Astrocytes and Regulates Neuronal Support Function Through Interaction with Npas3.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2025-01-09 DOI:10.3390/ncrna11010002
Sophie Schröder, M Sadman Sakib, Dennis M Krüger, Tonatiuh Pena, Susanne Burkhardt, Anna-Lena Schütz, Farahnaz Sananbenesi, André Fischer
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Abstract

Aging leads to cognitive decline and increased risk of neurodegenerative diseases. While molecular changes in central nervous system (CNS) cells contribute to this decline, the mechanisms are not fully understood. Long non-coding RNAs (lncRNAs) are key regulators of cellular functions. Background/Objectives: The roles of lncRNAs in aging, especially in glial cells, are not well characterized. Methods: We investigated lncRNA expression in non-neuronal cells from aged mice and identified 3222401L13Rik, a previously unstudied lncRNA, as upregulated in astrocytes during aging. Results: Knockdown of 3222401L13Rik in primary astrocytes revealed its critical role in regulating genes for neuronal support and synapse organization, a function conserved in human iPSC-derived astrocytes. A 3222401L13Rik interacts with the transcription factor Neuronal PAS Domain Protein 3 (Npas3), and overexpression of Npas3 rescues deficits in astrocytes lacking 3222401L13Rik. Conclusions: These data suggest that 3222401L13Rik upregulation may help delay age-related cognitive decline.

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LncRNA 3222401L13Rik在衰老星形胶质细胞中上调并通过与Npas3相互作用调节神经元支持功能
衰老会导致认知能力下降,并增加神经退行性疾病的风险。虽然中枢神经系统(CNS)细胞的分子变化有助于这种衰退,但其机制尚不完全清楚。长链非编码rna (lncrna)是细胞功能的关键调控因子。背景/目的:lncrna在衰老中的作用,特别是在神经胶质细胞中的作用尚未得到很好的表征。方法:我们研究了衰老小鼠非神经元细胞中lncRNA的表达,发现了一种之前未被研究过的lncRNA 3222401L13Rik在衰老过程中在星形胶质细胞中表达上调。结果:在原代星形胶质细胞中敲低3222401L13Rik,揭示了其在调节神经元支持和突触组织基因中的关键作用,这一功能在人类ipsc来源的星形胶质细胞中保守。3222401L13Rik与转录因子神经元PAS结构域蛋白3 (Npas3)相互作用,Npas3的过表达可以弥补星形胶质细胞缺乏3222401L13Rik的缺陷。结论:这些数据表明,3222401L13Rik上调可能有助于延缓与年龄相关的认知能力下降。
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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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