RNA Biology (Dec 2024)

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

  • Christy Montano,
  • Sergio Covarrubias,
  • Eric Malekos,
  • Sol Katzman,
  • Susan Carpenter

DOI
https://doi.org/10.1080/15476286.2024.2417155
Journal volume & issue
Vol. 21, no. 1
pp. 39 – 51

Abstract

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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.

Keywords