Biomolecules Interacting with Long Noncoding RNAs

Abstract

This review explores the complex interactions between long noncoding RNAs (lncRNAs) and other biomolecules, highlighting their pivotal roles in gene regulation and cellular function. LncRNAs, defined as RNA transcripts exceeding 200 nucleotides without encoding proteins, are involved in diverse biological processes, from embryogenesis to pathogenesis. They interact with DNA through mechanisms like triplex structure formation, influencing chromatin organization and gene expression. LncRNAs also modulate RNA-mediated processes, including mRNA stability, translational control, and splicing regulation. Their versatility stems from their forming of complex structures that enable interactions with various biomolecules. This review synthesizes current knowledge on lncRNA functions, discusses emerging roles in development and disease, and evaluates potential applications in diagnostics and therapeutics. By examining lncRNA interactions, it provides insights into the intricate regulatory networks governing cellular processes, underscoring the importance of lncRNAs in molecular biology. Unlike the majority of previous reviews that primarily focused on individual aspects of lncRNA biology, this comprehensive review uniquely integrates structural, functional, and mechanistic perspectives on lncRNA interactions across diverse biomolecules. Additionally, this review critically evaluates cutting-edge methodologies for studying lncRNA interactions, bridges fundamental molecular mechanisms with potential clinical applications, and highlights their potential.

Keywords: RNA–DNA triplexes; cellular function; gene regulation; long noncoding RNA; miRNA sponge.

Figure 1

Schematic representation of the nuclear localization and functions of four representative lncRNAs. (A) MEG3: MEG3 is a nuclear-retained lncRNA that interacts with the Polycomb Repressive Complex 2 (PRC2) to regulate gene expression through chromatin modification. (B) TERRA: TERRA is a telomeric repeat-containing RNA that localizes to telomeres and interacts with various telomere-associated proteins, playing a crucial role in telomere maintenance and genome stability. (C) CCAT1-L: CCAT1-L is a nuclear lncRNA involved in the regulation of chromatin architecture and gene expression, particularly at the MYC locus, by mediating long-range chromatin interactions. (D) FIRRE: FIRRE is a lncRNA that localizes to the nuclear matrix and is implicated in the organization of higher-order chromatin structure by interacting with multiple genomic loci across different chromosomes.

Figure 2

Schematic representation of the diverse regulatory functions of lncRNAs in gene expression. (A) BACE1-AS: BACE1 antisense RNA (BACE1-AS) protects BACE1 mRNA from microRNA (miRNA)-mediated degradation, thereby stabilizing BACE1 mRNA and enhancing its expression. (B) AS Uchl1: Antisense Uchl1 (AS Uchl1) accelerates the translation of Uchl1 mRNA, promoting increased protein synthesis. (C) H19: The lncRNA H19 modulates the expression of Wnt5a mRNA, illustrating its role in post-transcriptional gene regulation. (D) MALAT1: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates alternative splicing of pre-mRNAs, thereby influencing mRNA maturation and diversity.

Figure 3

Schematic representation of the molecular mechanisms and cellular functions of four representative lncRNAs. (A) HOTAIR: HOTAIR acts as a scaffold for chromatin-modifying complexes, such as PRC2 and LSD1, leading to epigenetic gene silencing and regulation of gene expression. (B) PARTICLE: PARTICLE is involved in the regulation of gene expression in response to environmental stress, functioning through interactions with chromatin and modulation of transcriptional activity. (C) PANDA: PANDA interacts with transcription factors and regulatory proteins to inhibit apoptosis and promote cell survival, particularly in response to DNA damage. (D) SRA: SRA serves as a coactivator for nuclear receptors and other transcription factors, facilitating the regulation of gene transcription and influencing diverse cellular processes.