Role of RNA as Regulator, Therapeutic Target and Probe for Early Disease Diagnosis

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 949

Special Issue Editor


E-Mail Website
Guest Editor
1. Department of Medical and Molecular Sciences, University of Delaware, Newark, DE 19716, USA
2. Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
3. Department of Plant and Soil Sciences, University of Delaware, Newark, DE 19716, USA
Interests: RNA biology; single-molecule RNA imaging; regulation of transcription; post-transcriptional modification; non-coding RNA; Ewing's sarcoma; cerebral palsy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The emergence of high-throughput sequencing technologies has enabled researchers to explore the complex landscape of cellular RNA molecules, including both coding and non-coding species. It is evident that RNA is not only a messenger of genetic information but that it also plays crucial roles in various biological processes, such as gene expression regulation, cell cycle control, and responses to stress stimuli.

This Special Issue explores the regulatory roles of both coding and non-coding RNAs and their potential to serve as sensitive and specific biomarkers for the early detection, progression, and therapeutic monitoring of a wide array of diseases. In addition to their potential as diagnostic and prognostic markers, coding and non-coding RNAs are also being explored as therapeutic targets for various disorders. 

Overall, this Special Issue aims to delves into the pivotal role of RNA molecules in the cellular landscape, particularly in the context of various disorders. By understanding the complex interplay between these molecules and cellular function, researchers can develop novel diagnostic tools and therapeutic strategies for a wide range of diseases. 

To address these topics, we will welcome original research articles or state-of-the-art reviews on using RNA molecules as regulators and biomarkers to monitor disorders at the cellular level. 

Dr. Mona Batish
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • coding RNAs
  • non-coding RNAs (ncRNAs)
  • regulatory RNAs
  • RNA-based diagnostics
  • disease biomarkers
  • RNA monitoring techniques
  • molecular probes
  • RNA interference (RNAi)

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

22 pages, 5264 KB  
Article
RXR-Mediated Remodeling of Transcriptional and Chromatin Landscapes in APP Mouse Brain: Insights from Integrated Single-Cell RNA and ATAC Profiling
by Yi Lu, Xuebao Wang, Carolina Saibro-Girardi, Nicholas Francis Fitz, Radosveta Koldamova and Iliya Lefterov
Cells 2025, 14(24), 1970; https://doi.org/10.3390/cells14241970 - 11 Dec 2025
Abstract
Ligand-activated Retinoid X Receptors (RXRs) regulate gene networks essential for neural development, neuroinflammation, and metabolism. Understanding how RXR activation influences chromatin architecture and gene expression may reveal mechanisms relevant to neurodegenerative diseases. We used Bexarotene-treated APP/PS1ΔE9 mice to study RXR-mediated regulatory mechanisms by [...] Read more.
Ligand-activated Retinoid X Receptors (RXRs) regulate gene networks essential for neural development, neuroinflammation, and metabolism. Understanding how RXR activation influences chromatin architecture and gene expression may reveal mechanisms relevant to neurodegenerative diseases. We used Bexarotene-treated APP/PS1ΔE9 mice to study RXR-mediated regulatory mechanisms by integrating single-nucleus ATAC-seq (snATAC-seq) with single-cell RNA-seq (scRNA-seq) and validating differentially accessible chromatin peaks using RXR ChIP-seq. Transcription factor (TF) footprinting analysis mapped regulatory networks activated by ligand-bound RXR. Our integrated analyses revealed a multilayered transcriptional cascade initiated by RXR signaling. We identified RXR-centered regulatory circuits involving heterodimer activation, upregulation of downstream TFs, and induction of metabolic pathways relevant to neural function. Detailed analysis of neuronal TF networks revealed that Bexarotene modulates RXR’s role through existing regulatory scaffolds rather than creating new ones. This study demonstrates that combining scRNA-seq, snATAC-seq, and ChIP-seq enables comprehensive analysis of RXR-mediated transcriptional regulation. RXR activation orchestrates cell-type-specific chromatin remodeling of gene networks controlling neuroinflammation, lipid metabolism, and synaptic signaling, providing mechanistic insights into RXR-dependent transcriptional programs in Alzheimer’s disease pathology. Full article
Show Figures

Figure 1

12 pages, 1875 KB  
Article
CRISPR Disruption of scaRNA1 Reduces Pseudouridylation in Spliceosomal RNA U2 at U89 and Perturbs the Transcriptome in HEK293T Cells
by Amanda Gardner-Kay, Lynndy Le, Michael Filla, Nataliya Kibiryeva, James E. O’Brien, Jr. and Douglas C. Bittel
Cells 2025, 14(23), 1882; https://doi.org/10.3390/cells14231882 - 27 Nov 2025
Viewed by 271
Abstract
Small Cajal body-associated RNAs (scaRNAs) are essential for biochemical modification of spliceosomal RNAs and spliceosome function. Changes in scaRNA expression level have been associated with developmental issues, including cancer and congenital heart defects (CHDs), although the mechanism remains unclear. Small Cajal body-associated RNA [...] Read more.
Small Cajal body-associated RNAs (scaRNAs) are essential for biochemical modification of spliceosomal RNAs and spliceosome function. Changes in scaRNA expression level have been associated with developmental issues, including cancer and congenital heart defects (CHDs), although the mechanism remains unclear. Small Cajal body-associated RNA 1 (scaRNA1) guides pseudouridylation at uridine 89 (Ψ89) of the spliceosomal RNA U2, a highly conserved modification that may be critical for spliceosome function. To investigate the role of scaRNA1 in splicing regulation, CRISPR-Cas9 genome editing was used to introduce targeted deletions in the scaRNA1 locus in HEK293T cells. Edited clones were identified by T7 endonuclease I assay and confirmed by Sanger sequencing. Pseudouridylation at Ψ89 was quantified using CMC-based reverse transcription followed by quantitative PCR, and global mRNA splicing alterations were assessed by RNA sequencing. Clones harboring scaRNA1 disruptions exhibited a significant reduction in Ψ89 pseudouridylation, consistent with impaired scaRNA1 function. Transcriptome analysis (of mRNA from two clones) revealed >300 protein coding genes with significant changes in transcript isoform level, including >100 genes related to RNA-binding activity. These results indicate that scaRNA1 disruption alters spliceosomal function and leads to substantial changes in mRNA splicing. The dysregulated splicing of RNA-binding proteins may impair RNA processing and gene expression programs required for normal development, providing new insight into how noncoding RNA dysfunction may contribute to developmental pathogenesis. Full article
Show Figures

Figure 1

24 pages, 3622 KB  
Article
Manipulating PARK7/DJ-1 Levels by Genotoxic Stress Alters Noncoding RNAs and Cellular Homeostasis
by Keren Zohar, Haya Zoubi, Michal Goldberg, Tsiona Eliyahu and Michal Linial
Cells 2025, 14(23), 1860; https://doi.org/10.3390/cells14231860 - 25 Nov 2025
Viewed by 210
Abstract
DJ-1/PARK7 is a multifunctional protein that plays a vital role in sensing oxidative stress and maintaining redox homeostasis. As an oncogene, DJ-1 influences p53-mediated stress responses and contributes to cancer progression. This study investigates the impact of X-ray-induced DNA breaks on cellular responses [...] Read more.
DJ-1/PARK7 is a multifunctional protein that plays a vital role in sensing oxidative stress and maintaining redox homeostasis. As an oncogene, DJ-1 influences p53-mediated stress responses and contributes to cancer progression. This study investigates the impact of X-ray-induced DNA breaks on cellular responses under varying DJ-1 expression levels. Using siRNA knockdown and overexpression approaches, transcriptional changes were analyzed by RNA-seq. Naïve cells exhibited only a moderate response to X-ray exposure, including suppression of the cell cycle and activation of stress pathways. In contrast, DJ-1 overexpression caused pronounced gene-expression suppression, particularly affecting ribosomal genes and mitochondria, with 21- and 3.5-fold enrichment, respectively. DJ-1 knockdown led to extensive, non-specific transcriptional changes affecting ~18% of all transcripts (~3400), indicating disrupted cellular homeostasis. Under DJ-1 knockdown, X-ray irradiation resulted in a 3.7-fold enrichment of suppressed DNA-damage response genes. Notably, approximately 25% of non-coding RNAs (ncRNAs) were differentially expressed following DJ-1 manipulation. X-ray-irradiated cells with DJ-1 overexpression also showed reduced expression of SNHG lncRNAs that host snoRNAs, potentially altering miRNA-sponging capacity and ribosomal regulation. These findings underscore DJ-1’s critical role in modulating cellular responses to genotoxic stress, reshaping transcriptional landscapes, and regulating ncRNA profiles. The dual impact of DJ-1 on redox and transcriptional networks positions it as a potential therapeutic target in diseases involving oxidative stress and impaired DNA repair. Full article
Show Figures

Graphical abstract

Back to TopTop