Identification and functional characterization of lncRNAs involved in human monocyte-to-macrophage differentiation

Although long noncoding RNAs (lncRNAs) constitute the majority of the human transcriptome, the functional roles of most remain elusive. While protein-coding genes in macrophage biology have been extensively studied, the contribution of lncRNAs in this context is poorly understood. Given the vast num...

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Bibliographic Details
Main Authors: Christy Montano, Sergio Covarrubias, Eric Malekos, Sol Katzman, Susan Carpenter
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:RNA Biology
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Online Access:https://www.tandfonline.com/doi/10.1080/15476286.2024.2417155
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Summary:Although long noncoding RNAs (lncRNAs) constitute the majority of the human transcriptome, the functional roles of most remain elusive. While protein-coding genes in macrophage biology have been extensively studied, the contribution of lncRNAs in this context is poorly understood. Given the vast number of lncRNAs (>20,000), identifying candidates for functional characterization poses a significant challenge. Here, we present two complementary approaches to pinpoint and investigate lncRNAs involved in monocyte-to-macrophage differentiation: RNA-seq for functional inference and a high-throughput functional screen. These strategies enabled us to identify four lncRNA regulators of monocyte differentiation: lincRNA-JADE1, lincRNA-ANXA3, GATA2-AS1, and PPP2R5C-AS1. Preliminary insights suggest these lncRNAs may act in cis through neighbouring protein-coding genes, although their precise mechanisms remain to be elucidated. We further discuss the strengths and weaknesses of these methodologies, along with validation pipelines crucial for establishing lncRNA functionality.
ISSN:1547-6286
1555-8584