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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.
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http://dx.doi.org/10.3390/biom15060881 | DOI Listing |
Targets (Basel)
September 2025
Medicine and Oncology ISU, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA.
Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we explore reports and strategies for the proteomic characterization of lncRNA-associated proteins, particularly emphasizing high-throughput liquid chromatography-mass spectrometry (LC-MS)-based techniques.
View Article and Find Full Text PDFBrief Bioinform
July 2025
Department of Biological Sciences, Bose Institute, Unified Academic Campus, Kolkata 700 091, West Bengal, India.
Long noncoding RNA (lncRNA)-protein Interaction (LPI) across diverse biological systems, directly and indirectly, regulates various cellular processes. Experimental assays to recognize the protein binding partners of lncRNAs are highly time-consuming and expensive. In silico predictive approaches involving pattern recognition techniques provide a promising alternative to it by reducing the search space.
View Article and Find Full Text PDFJ Proteome Res
September 2025
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Long noncoding RNAs (lncRNAs) exert regulatory functions in a wide spectrum of biological contexts, and certain regulatory functions involve the formation of RNA-protein complexes. Discovering the structure and function of these complexes may unveil important functional insights. The gene encoding the DEAD-box RNA helicase 41 protein (DDX41) is subject to extensive germline genetic variation, and certain variants create a predisposition to develop myelodysplastic syndrome and acute myeloid leukemia.
View Article and Find Full Text PDFInt J Genomics
July 2025
Department of Geriatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Long noncoding RNA (lncRNA) CASC, crucial in colorectal cancer (CRC) progression, remains largely unexplored despite its potential. The CRC data comes from The Cancer Genome Atlas (TCGA) database. The limma package was used to screen differentially expressed genes (DEGs), intersecting with CASC genes that yielded key hub lncRNAs.
View Article and Find Full Text PDFBrain Res
September 2025
School of Mathematics, Harbin Institute of Technology, Harbin 150001, China. Electronic address:
Parkinson's disease (PD) pathogenesis involves dopaminergic neuron loss, yet the role of long non-coding RNAs (lncRNAs) remains poorly characterized. In this study, we perform a comprehensive meta-analysis of PD transcriptomes, identifying the top 50 significantly dysregulated lncRNAs (25 upregulated including NEAT1 and LINC00869; 25 downregulated including CASC2 and HULC) from 718 differentially expressed lncRNAs. Through functional enrichment analyses, we demonstrate that upregulated lncRNAs predominantly regulate neuroinflammatory pathways (NEAT1-NF-κB), α-synuclein aggregation (HOTAIR), regulation of gene expression epigenetic (MEG3) and vesicle trafficking (LINC00869), while downregulated lncRNAs control apoptotic signaling (CASC2-MAPK), lysosomal function (SFTA3), and metabolic homeostasis (HULC).
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