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Review
. 2025 Jun 17;15(6):881.
doi: 10.3390/biom15060881.

LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms

Affiliations
Review

LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms

Zuoneng Wang et al. Biomolecules. .

Abstract

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in a multitude of biological processes. However, their functional basis, particularly structure-based functional characteristics, remains elusive. lncRNAs exert their influence primarily through intricate interactions with various cellular components. Among these, interactions with proteins have garnered increasing attention. Recent research highlights the significance of the interactions with proteins as a plausible mechanism underlying lncRNA functions. Here, we delve into the interactions between lncRNAs and RNA-binding proteins (RBPs), explore their implications in cellular processes, and examine bioinformatic and experimental approaches for characterizing these interactions. We introduce an innovative ISD strategy to decipher the mysterious mechanism of lncRNAs. Through reviewing the recent advances in the study of proteins and their complexes, we incorporate the ISD strategy into our integrated structural analysis pipeline for comprehensively understanding the structure-function relationship of lncRNAs. Advances in the development of innovative therapeutic approaches based on lncRNA-protein interactions (LPIs) are reviewed accordingly.

Keywords: RNA-binding proteins; lncRNA-protein interactions; long non-coding RNA; structure-function relationship; therapeutic targets.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic illustration of major archetypes of LPIs (dashed boxes).
Figure 2
Figure 2
Recent uncovered lncRNA-protein partners and their associated diseases [,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,137,138,139,140,141,142,143,144,145,146,147,148,149].
Figure 3
Figure 3
Schematic description of current approaches for detecting LPI.
Figure 4
Figure 4
Illustration of current high-resolution 3D structural analysis methods for lncRNA-protein complexes.
Figure 5
Figure 5
Schematic diagram of proposed integrated structural analysis of lncRNA from the perspective of protein partners; the ISD strategy is incorporated into the pipeline.

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