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RNA Biology and Regulation

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 June 2025 | Viewed by 5636

Special Issue Editor

Special Issue Information

Dear Colleagues,

This research topic addresses many of the eukaryotic gene expression steps mediated by RNAs. In eukaryotes, many kinds of RNAs are transcribed from genome DNA. Transcribed RNA molecules undergo multiple post-transcriptional processes such as splicing, editing, modification, transport, translation, and degradation. In other cases, RNAs themselves are involved in the regulation of gene expression steps in eukaryotes. A defect, mis-regulation, or malfunction of RNA metabolism processes often result in genetic diseases in humans.

As the Guest Editor of this Special Issue of IJMS, entitled “RNA Biology and Regulation”, I welcome submissions from many researchers working on the wide spectrum of biological and physiological processes in which RNAs are involved in higher eukaryotes. This Special Issue aims to gather manuscripts that address various RNA metabolism processes, such as transcription, splicing, editing, modification, transport, localization, translation, and degradation. Examples of topics for this Special Issue include both the basic science—elucidation of molecular mechanisms for RNA regulation—and the implications and applications for therapeutic approaches of human diseases. Manuscripts focusing on the potential role of RNAs in the diagnosis and therapy of RNA are also welcome. Formats suitable for submissions include original research reports, reviews, perspectives/opinions, and methodology articles.

Dr. Naoyuki Kataoka
Guest Editor

Manuscript Submission Information

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Keywords

  • RNA processing
  • RNA transport
  • RNA localization
  • RNA editing
  • RNA synthesis
  • RNA stability
  • RNA modification
  • translation
  • transcription
  • RNA metabolism
  • human diseases

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Published Papers (6 papers)

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Research

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14 pages, 1609 KiB  
Article
SRSF9-Mediated Exon Recognition Promotes Exon 2 Inclusion in Mecp2 Pre-mRNA Alternative Splicing
by Saya Oshizuki, So Masaki, Satoshi Tanaka and Naoyuki Kataoka
Int. J. Mol. Sci. 2025, 26(7), 3319; https://doi.org/10.3390/ijms26073319 - 2 Apr 2025
Viewed by 303
Abstract
Alternative splicing is one of the processes that contributes to producing a vast protein diversity from the limited number of protein-coding genes in higher eukaryotes. The Methyl CpG Binding Protein 2 (Mecp2) gene, whose mutations cause Rett syndrome, generates two protein [...] Read more.
Alternative splicing is one of the processes that contributes to producing a vast protein diversity from the limited number of protein-coding genes in higher eukaryotes. The Methyl CpG Binding Protein 2 (Mecp2) gene, whose mutations cause Rett syndrome, generates two protein isoforms, MeCP2E1 and MeCP2E2, by alternative splicing. These isoforms likely possess non-redundant functions. However, the molecular mechanism for Mecp2 pre-mRNA alternative splicing remains to be understood. Here, we analyzed the alternative splicing mechanism of MeCP2 pre-mRNA and found that exon 2 is efficiently recognized through adjacent strong splice sites. In addition, exonic splicing enhancer (ESE) in exon 2 plays an important role in exon 2 inclusion, which is highly likely to be mediated by SRSF9. Full article
(This article belongs to the Special Issue RNA Biology and Regulation)
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15 pages, 2834 KiB  
Article
Mitochondrial Small RNA Alterations Associated with Increased Lysosome Activity in an Alzheimer’s Disease Mouse Model Uncovered by PANDORA-seq
by Xudong Zhang, Junchao Shi, Pratish Thakore, Albert L. Gonzales, Scott Earley, Qi Chen, Tong Zhou and Yumei Feng Earley
Int. J. Mol. Sci. 2025, 26(7), 3019; https://doi.org/10.3390/ijms26073019 - 26 Mar 2025
Viewed by 299
Abstract
Emerging small non-coding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, such as internal and terminal modifications, [...] Read more.
Emerging small non-coding RNAs (sncRNAs), including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), are critical in various biological processes, such as neurological diseases. Traditional sncRNA-sequencing (seq) protocols often miss these sncRNAs due to their modifications, such as internal and terminal modifications, that can interfere with sequencing. We recently developed panoramic RNA display by overcoming RNA modification aborted sequencing (PANDORA-seq), a method enabling comprehensive detection of modified sncRNAs by overcoming the RNA modifications. Using PANDORA-seq, we revealed a previously unrecognized sncRNA profile enriched by tsRNAs/rsRNAs in the mouse prefrontal cortex and found a significant downregulation of mitochondrial tsRNAs and rsRNAs in an Alzheimer’s disease (AD) mouse model compared to wild-type controls, while this pattern is not present in the genomic tsRNAs and rsRNAs. Moreover, our integrated analysis of gene expression and sncRNA profiles reveals that those downregulated mitochondrial sncRNAs negatively correlate with enhanced lysosomal activity, suggesting a crucial interplay between mitochondrial RNA dynamics and lysosomal function in AD. Given the versatile tsRNA/tsRNA molecular actions in cellular regulation, our data provide insights for future mechanistic study of AD with potential therapeutic strategies. Full article
(This article belongs to the Special Issue RNA Biology and Regulation)
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14 pages, 2886 KiB  
Article
Advanced Prediction of Hepatic Oncogenic Transformation in HBV Patients via RNA-Seq Data Analysis and Deep Learning Techniques
by Zhengtai Li, Lei Huang and Changyuan Yu
Int. J. Mol. Sci. 2024, 25(18), 9827; https://doi.org/10.3390/ijms25189827 - 11 Sep 2024
Viewed by 1186
Abstract
Liver cancer, recognized as a significant global health issue, is increasingly correlated with Hepatitis B virus (HBV) infection, as evidenced by numerous scientific studies. This study aims to examine the correlation between HBV infection and the development of liver cancer, focusing on using [...] Read more.
Liver cancer, recognized as a significant global health issue, is increasingly correlated with Hepatitis B virus (HBV) infection, as evidenced by numerous scientific studies. This study aims to examine the correlation between HBV infection and the development of liver cancer, focusing on using RNA sequencing (RNA-seq) to detect HBV sequences and applying deep learning techniques to estimate the likelihood of oncogenic transformation in individuals with HBV. Our study utilized RNA-seq data and employed Pathseq software and sophisticated deep learning models, including a convolutional neural network (CNN), to analyze the prevalence of HBV sequences in the samples of patients with liver cancer. Our research successfully identified the prevalence of HBV sequences and demonstrated that the CNN model achieved an exceptional Area Under the Curve (AUC) of 0.998 in predicting cancerous transformations. We observed no viral synergism that enhanced the pathogenicity of HBV. A detailed analysis of sequences misclassified by the CNN model revealed that longer sequences were more conducive to accurate recognition. The findings from this study provide critical insights into the management and prognosis of patients infected with HBV, highlighting the potential of advanced analytical techniques in understanding the complex interactions between viral infections and cancer development. Full article
(This article belongs to the Special Issue RNA Biology and Regulation)
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17 pages, 3643 KiB  
Article
Comprehensive Transcriptome Analysis Expands lncRNA Functional Profiles in Breast Cancer
by Wenyong Zhu, Hao Huang, Zixi Hu, Yu Gu, Rongxin Zhang, Huiling Shu, Hongjia Liu and Xiao Sun
Int. J. Mol. Sci. 2024, 25(15), 8456; https://doi.org/10.3390/ijms25158456 - 2 Aug 2024
Cited by 1 | Viewed by 1547
Abstract
Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker [...] Read more.
Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention. Full article
(This article belongs to the Special Issue RNA Biology and Regulation)
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Review

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24 pages, 1492 KiB  
Review
Fine Regulation of MicroRNAs in Gene Regulatory Networks and Pathophysiology
by Mayu Seida, Koichi Ogami, Seiko Yoshino and Hiroshi I. Suzuki
Int. J. Mol. Sci. 2025, 26(7), 2861; https://doi.org/10.3390/ijms26072861 - 21 Mar 2025
Viewed by 476
Abstract
MicroRNAs (miRNAs) are ~22-nucleotide small non-coding RNAs that play critical roles in gene regulation. The discovery of miRNAs in Caenorhabditis elegans in 1993 by the research groups of Victor Ambros and Gary Ruvkun opened a new era in RNA research. Typically, miRNAs act [...] Read more.
MicroRNAs (miRNAs) are ~22-nucleotide small non-coding RNAs that play critical roles in gene regulation. The discovery of miRNAs in Caenorhabditis elegans in 1993 by the research groups of Victor Ambros and Gary Ruvkun opened a new era in RNA research. Typically, miRNAs act as negative regulators of gene expression by binding to complementary sequences within the 3′ untranslated regions of their target mRNAs. This interaction results in translational repression and/or target destabilization. The expression levels and activities of miRNAs are fine-tuned by multiple factors, including the miRNA biogenesis pathway, variability in target recognition, super-enhancers, post-transcriptional modifications, and target-directed miRNA degradation. Together, these factors form complex mechanisms that govern gene regulation and underlie several pathological conditions, including Argonaute syndrome, genetic diseases driven by super-enhancer-associated miRNAs, and miRNA-deadenylation-associated bone marrow failure syndromes. In addition, as miRNA genes have evolved rapidly in vertebrates, miRNA regulation in the brain is characterized by several unique features. In this review, we summarize recent insights into the role of miRNAs in human diseases, focusing on miRNA biogenesis; regulatory mechanisms, such as super-enhancers; and the impact of post-transcriptional modifications. By exploring these mechanisms, we highlight the intricate and multifaceted roles of miRNAs in health and disease. Full article
(This article belongs to the Special Issue RNA Biology and Regulation)
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18 pages, 871 KiB  
Review
The Role of Long Non-Coding RNA in Rheumatoid Arthritis
by Kajetan Kiełbowski, Maciej Ćmil, Wojciech Jerzy Biniek, Estera Bakinowska and Andrzej Pawlik
Int. J. Mol. Sci. 2025, 26(2), 560; https://doi.org/10.3390/ijms26020560 - 10 Jan 2025
Viewed by 1214
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint damage and physical dysfunction. The pathogenesis of RA is highly complex, involving genetic, epigenetic, immune, and metabolic factors, among others. Over the years, research has highlighted the importance of non-coding RNAs [...] Read more.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint damage and physical dysfunction. The pathogenesis of RA is highly complex, involving genetic, epigenetic, immune, and metabolic factors, among others. Over the years, research has highlighted the importance of non-coding RNAs (ncRNAs) in regulating gene expression. Given their dysregulation in numerous conditions, ncRNAs are thought to play a role in pathological processes. In RA, aberrant levels of circulating long ncRNAs (lncRNAs) are commonly observed in peripheral blood, along with their dysregulated expression in peripheral blood mononuclear cells and synovial tissue. This review discusses the involvement of lncRNAs in inflammation and the aggressive characteristics of fibroblast-like synoviocytes, a key cellular population driving RA progression. Full article
(This article belongs to the Special Issue RNA Biology and Regulation)
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