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

Non-Coding RNA, Journal Year: 2025, Volume and Issue: 11(1), P. 2 - 2

Published: Jan. 9, 2025

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

Language: Английский

LncRNA 3222401L13Rik Is Up-regulated in Aging Astrocytes and Regulates Neuronal Support Function Through Interaction with Npas3

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

Abstract Aging is linked to a decline in cognitive functions and significantly increases the risk of neurodegenerative diseases. While molecular changes all central nervous system (CNS) cell types contribute aging-related decline, mechanisms driving disease development or offering protection remain poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators cellular gene expression, yet their roles aging, particularly within glial cells, are not well characterized. In this study, we investigated lncRNA expression profiles non-neuronal cells from aged mice. We identified 3222401L13Rik, previously unstudied enriched being specifically upregulated astrocytes during aging. Knockdown 3222401L13Rik primary revealed its critical role regulating genes essential for neuronal support synapse organization. This function was also conserved human iPSC-derived astrocytes. Additionally, found that mediates effects through interaction with transcription factor Neuronal PAS Domain Protein 3 (Npas3), overexpression Npas3 effectively rescued functional deficits observed lacking 3222401L13Rik. Our findings suggest upregulation aging acts compensatory mechanism enhance synaptic support, potentially delaying onset structural both neurons. Strategies boost earlier life may help mitigate age-associated loss plasticity.

Language: Английский

Huntingtin interactome reveals huntingtin role in regulation of double strand break DNA damage response (DSB/DDR), chromatin remodeling and RNA processing pathways

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Abstract Huntington’s Disease (HD), a progressive neurodegenerative disorder with no disease-modifying therapies, is caused by CAG repeat expansion in the HD gene encoding polyglutamine-expanded huntingtin (HTT) protein. Mechanisms of cellular pathogenesis and functions normal mutant HTT proteins are still not completely understood. protein has numerous interaction partners, it likely provides scaffold for assembly multiprotein complexes many which may be altered HD. Previous studies have implicated DNA damage response pathogenesis. Gene transcription RNA processing also emerged as molecular mechanisms associated Here we used multiple approaches to identify interactors context stress. Our results indicate that interacts involved regulation interconnected repair/remodeling pathways. We present evidence role double strand break repair mechanism. demonstrate functional major kinase DNA-PKcs association both nuclear speckles. show S1181 phosphorylation regulated DSB, can carried out (at least vitro ) DNA-PK. Furthermore, interactions binding speckles, including two encoded genes at modifier loci, TCERG1 MED15, chromatin remodeling complex BAF. These position an important scaffolding intermediary providing integrated expression mechanisms.

Language: Английский