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RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 30 July 2025 | Viewed by 10618

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Dr. Rosemary Kiernan

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Institut de Génétique Humaine, UMR 9002, CNRS, Université de Montpellier, Gene Regulation Laboratory, 141, rue de la Cardonille, 34396 Montpellier, France
Interests: transcription; ncRNAs; miRNAs; HIV; cancer
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Special Issue Information

Dear Colleagues,

RNA Biology: Unraveling the Complex Interplay between Proteins and RNAs in Gene Expression and Regulation delves into the intricate dance between proteins and RNAs in the complex world of gene expression and regulation. This Special Issue will explore the latest advancements in our collective understanding of the diverse roles of RNAs, from their transcriptional genesis to their post-transcriptional modifications, in shaping cellular function. We highlight the complexity of interactions between RNAs and proteins, including RNA-binding proteins, which orchestrate gene expression patterns and cellular responses. Furthermore, we encourage cutting-edge research on the emerging role of non-coding RNAs in gene regulation, epigenetic modifications, and disease pathogenesis. Through these studies, we can gain better insight into the dynamic and multifaceted nature of RNA biology, paving the way for future therapeutic interventions and biotechnological applications.

Dr. Rosemary Kiernan
Guest Editor

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Keywords

RNA biology
protein–RNA interplay
gene expression
post-transcriptional modifications
non-coding RNAs

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Published Papers (7 papers)

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Research

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14 pages, 2999 KiB

Open AccessArticle

Downregulated Expression of miR-200c-3p in Plasma Exosome as a Potential Biomarker in Takayasu’s Arteritis

by Lihong Du, Chenglong Fang, Biqing Huang, Xiaofeng Zeng, Jing Li and Xinping Tian

Int. J. Mol. Sci. 2025, 26(7), 2881; https://doi.org/10.3390/ijms26072881 - 22 Mar 2025

Viewed by 305

Abstract

Our previous work identified several differentially expressed miRNAs (DEmiRNAs) in plasma exosomes from Takayasu’s arteritis (TAK) patients. This study aimed to validate these findings and explore the correlation between DEmiRNAs and clinical parameters in untreated TAK. Plasma exosomes were isolated from 30 untreated TAK patients and 20 healthy controls. qPCR was used to quantify miR-34a-5p, miR-143-3p, miR-22-3p, miR-200c-3p, and miR-21-5p expression. Correlations between miRNA levels, clinical data, inflammation markers, and T helper cell frequencies were analyzed. The target genes of validated DEmiRNAs were identified using mirDIP, and pathway enrichment analysis was performed using GO/KEGG. The effect of validated DEmiRNAs on the MAPK pathway and proliferation in human aortic endothelial cells (HAECs) was investigated in vitro. Only miR-200c-3p expression was validated as significantly downregulated in plasma exosomes from untreated TAK patients. Lower miR-200c-3p levels correlated negatively with ITAS-2010 scores and were associated with relapsed disease. MiR-200c-3p levels also negatively correlated with circulating Th17.1 cell frequencies. In vitro, the TAK exosome treatment activated ERK1/2 and JNK pathways and promoted HAEC proliferation, which was inhibited by the miR-200c-3p mimic. The pathway enrichment analysis showed that the MAPK pathway may be involved. This study confirms the reduced miR-200c-3p expression in plasma exosomes from TAK patients, suggesting its potential as a biomarker for vascular inflammation. MiR-200c-3p may exert protective effects in TAK by suppressing MAPK pathway activation and EC proliferation. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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35 pages, 12488 KiB

Open AccessArticle

LncSL: A Novel Stacked Ensemble Computing Tool for Subcellular Localization of lncRNA by Amino Acid-Enhanced Features and Two-Stage Automated Selection Strategy

by Lun Zhu, Hong Chen and Sen Yang

Int. J. Mol. Sci. 2024, 25(24), 13734; https://doi.org/10.3390/ijms252413734 - 23 Dec 2024

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Abstract

Long non-coding RNA (lncRNA) is a non-coding RNA longer than 200 nucleotides, crucial for functions like cell cycle regulation and gene transcription. Accurate localization prediction from sequence information is vital for understanding lncRNA’s biological roles. Computational methods offer an effective alternative to traditional experimental methods for annotating lncRNA subcellular positions. Existing machine learning-based methods are limited and often overlook regions with coding potential that affect the function of lncRNA. Therefore, we propose a new model called LncSL. For feature encoding, both lncRNA sequences and amino acid sequences from open reading frames (ORFs) are employed. And we selected the most suitable features by CatBoost and integrated them into a new feature set. Additionally, a voting process with seven feature selection algorithms identified the higher contributive features for training our final stacked model. Additionally, an automatic model selection strategy is constructed to find a better performance meta-model for assembling LncSL. This study specifically focuses on predicting the subcellular localization of lncRNA in the nucleus and cytoplasm. On two benchmark datasets called S1 and S2 datasets, LncSL outperformed existing methods by 6.3% to 12.3% in the Matthew’s correlation coefficient on a balanced test dataset. On an unbalanced independent test dataset sourced from S1, LncSL improved by 4.7% to 18.6% in the Matthew’s correlation coefficient, which further demonstrates that LncSL is superior to other compared methods. In all, this study presents an effective method for predicting lncRNA subcellular localization through enhancing sequence information, which is always overlooked by traditional methods, and addressing contributive meta-model selection problems, which can offer new insights for other bioinformatics problems. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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12 pages, 1369 KiB

Open AccessArticle

Investigating the Role of Primary Cilia and Bone Morphogenetic Protein Signaling in Periodontal Ligament Response to Orthodontic Strain In Vivo and In Vitro: A Pilot Study

by Emily R. Moore and Anna Konermann

Int. J. Mol. Sci. 2024, 25(23), 12648; https://doi.org/10.3390/ijms252312648 - 25 Nov 2024

Viewed by 870

Abstract

Periodontal ligament (PDL) cells are crucial for mechanosensation and mechanotransduction within the PDL, yet the role of primary cilia in orthodontic force transmission has not been examined. While bone morphogenetic protein (BMP) signaling significantly influences ciliary function, its effect on cellular responses to mechanical stress has not been investigated. This study aims to investigate whether primary cilia and BMP signaling are involved in the periodontal ligament’s response to orthodontic tooth movement and the resultant mechanical strain. To visualize primary cilia, human PDL cells were cultured on glass-bottom dishes for five days, with a subset fixed daily, followed by immunostaining with anti-acetylated α-tubulin and Alexa Fluor 568 and imaging using a fluorescence microscope under 405 nm and 561 nm laser excitation. Human PDL cells were grown on Bioflex^® culture plates and subsequently exposed to static tensile strains of 2.5%, 5%, 10%, 20%, on a FX-6000T™ Tension System for 24 h. RT-qPCR was performed to evaluate changes in expression of primary cilia via Ift88 expression, mechanotransduction via Cox2 expression, and BMP signaling-related genes. Histological specimens from orthodontically loaded and control human premolars were investigated for primary cilia and BMP signaling using immunohistochemistry and confocal microscopy. Primary cilia were observed in PDL cells from day one, with their incidence and length increasing over time alongside cell density. BMP signaling components, including upregulated genes such as Bmp7 (10.99–14.97 fold), Alk2 (3.19–5.45 fold), and Bmpr2 (1.64–8.40 fold), consistently responded to strain, while Cox2 and Ift88 showed differential regulation depending on strain intensity. In vivo, orthodontic movement activated BMP signaling and increased primary cilium incidence in the PDL. These findings indicate the potential role of primary cilia and BMP signaling in the mechanosensitivity of PDL cells under orthodontic forces. Further studies are required to understand the complex mechanotransduction mechanisms and role of these components in cellular adaptation during orthodontic tooth movement. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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19 pages, 11576 KiB

Open AccessArticle

miR-107 Targets NSG1 to Regulate Hypopharyngeal Squamous Cell Carcinoma Progression through ERK Pathway

by Yifan Hu, Zhizhen He, Baoai Han, Zehua Lin, Peng Zhou, Shuang Li, Shuo Huang and Xiong Chen

Int. J. Mol. Sci. 2024, 25(11), 5961; https://doi.org/10.3390/ijms25115961 - 29 May 2024

Cited by 1 | Viewed by 1495

Abstract

Hypopharyngeal squamous cell carcinoma (HSCC) is a kind of malignant tumor with a poor prognosis and low quality of life in the otolaryngology department. It has been found that microRNA (miRNA) plays an important role in the occurrence and development of various tumors. This study found that the expression level of miRNA-107 (miR-107) in HSCC was significantly reduced. Subsequently, we screened out the downstream direct target gene Neuronal Vesicle Trafficking Associated 1 (NSG1) related to miR-107 through bioinformatics analysis and found that the expression of NSG1 was increased in HSCC tissues. Following the overexpression of miR-107 in HSCC cells, it was observed that miR-107 directly suppressed NSG1 expression, leading to increased apoptosis, decreased proliferation, and reduced invasion capabilities of HSCC cells. Subsequent experiments involving the overexpression and knockdown of NSG1 in HSCC cells demonstrated that elevated NSG1 levels enhanced cell proliferation, migration, and invasion, while the opposite effect was observed upon NSG1 knockdown. Further investigations revealed that changes in NSG1 levels in the HSCC cells were accompanied by alterations in ERK signaling pathway proteins, suggesting a potential regulatory role of NSG1 in HSCC cell proliferation, migration, and invasion through the ERK pathway. These findings highlight the significance of miR-107 and NSG1 in hypopharyngeal cancer metastasis, offering promising targets for therapeutic interventions and prognostic evaluations for HSCC. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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Review

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16 pages, 1331 KiB

Open AccessReview

Insights into the Mode and Mechanism of Interactions Between RNA and RNA-Binding Proteins

by Yan Fang, Xinyu Liu, Yuli Liu and Naiyi Xu

Int. J. Mol. Sci. 2024, 25(21), 11337; https://doi.org/10.3390/ijms252111337 - 22 Oct 2024

Viewed by 2556

Abstract

Both RNA and protein play important roles in the process of gene expression and regulation, and it has been widely discussed that the interactions between RNA and protein affect gene transcription, translation efficiency, and post-translational modification. As an important class of proteins, RNA-binding proteins bind to RNA and affect gene expression in various ways. Here, we review the structural and functional properties of RNA-binding proteins and illustrate the specific modes of interactions between RNA and RNA-binding proteins and describe the involvement of some representative RNA-binding protein families in this network of action. Furthermore, we also explore the association that exists between RNA-binding proteins and the onset of diseases, as well as their potential in terms of serving as a therapeutic tool for the treatment of diseases. The in-depth exploration of the interactions between RNA and RNA-binding proteins reveals the dynamic process of gene expression and regulation, as well as offering valuable insights to advance the progress in the dissection of disease mechanisms and research and discovery of drugs, which promote the development of molecular biology. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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16 pages, 1163 KiB

Open AccessReview

The Versatile Roles of nc886, a Fascinating and Peculiar Regulatory Non-Coding RNA, in Cancer

by Jiyoung Joan Jang, Dongmin Kang, Yeon-Su Lee and Yong Sun Lee

Int. J. Mol. Sci. 2024, 25(19), 10825; https://doi.org/10.3390/ijms251910825 - 9 Oct 2024

Viewed by 1157

Abstract

This review concerns nc886, a 101-nucleotide non-coding RNA (ncRNA). Because nc886 is transcribed by RNA polymerase III (Pol III) and contains a CpG island in its promoter region, its expression is regulated by several transcription factors and the DNA methylation status. These features drive nc886 expression in two opposing directions during tumorigenesis. The known function of nc886 is to bind to and modulate the activity of target proteins such as PKR, Dicer, and OAS1. By being differentially expressed during tumorigenesis and interacting with these proteins, nc886 plays a role in tumor surveillance, promotes or suppresses tumorigenesis, and influences the efficacy of cancer therapy. The multiple roles of nc886 have been well-documented in the literature. In this review, we have summarized this literature and critically discussed the roles and mechanisms of action of nc886 in various cancers. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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Other

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26 pages, 5387 KiB

Open AccessHypothesis

SARS-CoV-2 Displays a Suboptimal Codon Usage Bias for Efficient Translation in Human Cells Diverted by Hijacking the tRNA Epitranscriptome

by Patrick Eldin, Alexandre David, Christophe Hirtz, Jean-Luc Battini and Laurence Briant

Int. J. Mol. Sci. 2024, 25(21), 11614; https://doi.org/10.3390/ijms252111614 - 29 Oct 2024

Cited by 1 | Viewed by 1871

Abstract

Codon bias analysis of SARS-CoV-2 reveals suboptimal adaptation for translation in human cells it infects. The detailed examination of the codons preferentially used by SARS-CoV-2 shows a strong preference for Lys^AAA, Gln^CAA, Glu^GAA, and Arg^AGA, which are infrequently used in human genes. In the absence of an adapted tRNA pool, efficient decoding of these codons requires a 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²) modification at the U₃₄ wobble position of the corresponding tRNAs (tLys^UUU; tGln^UUG; tGlu^UUC; tArg^UCU). The optimal translation of SARS-CoV-2 open reading frames (ORFs) may therefore require several adjustments to the host’s translation machinery, enabling the highly biased viral genome to achieve a more favorable “Ready-to-Translate” state in human cells. Experimental approaches based on LC-MS/MS quantification of tRNA modifications and on alteration of enzymatic tRNA modification pathways provide strong evidence to support the hypothesis that SARS-CoV-2 induces U₃₄ tRNA modifications and relies on these modifications for its lifecycle. The conclusions emphasize the need for future studies on the evolution of SARS-CoV-2 codon bias and its ability to alter the host tRNA pool through the manipulation of RNA modifications. Full article

(This article belongs to the Special Issue RNA Biology: Unraveling the Complex Interplay Between Proteins and RNAs in Gene Expression and Regulation)

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