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Targeting Dysregulated RNA Processing in Disease
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Targeting Dysregulated RNA Processing in Disease

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: closed (31 March 2024) | Viewed by 4014

Special Issue Editor

Prof. Dr. Victor van Beusechem

E-Mail Website
Guest Editor
Department Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands
Interests: cancer therapy development; therapeutic target discovery; functional genetic screening; oncolytic immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Emerging data show that co-transcriptional and post-transcriptional modifications of protein-encoding messenger RNAs are important determinants of disease development and progression, response to treatment and drug resistance. Aberrant RNA methylation, splicing and editing affect mRNA transport and stability, as well as its translation into protein isoforms with distinct or even opposing functions. Alternative mRNA splicing products and loss of canonically spliced variants were shown to correlate with stage and progression in malignancy. Frequent somatic mutations in regulators of RNA modification and altered splicing patterns in key cancer-associated genes were found in cancer cells and have been proposed as a hallmark of cancer. A deeper understanding of the molecular mechanisms associated with dysregulated RNA modification and the study of altered RNA modification events can provide key insights into the pathophysiology of disease and pave the way for biomarker discovery and identification of novel therapeutic vulnerabilities. In particular small molecule inhibitors of alternative RNA splicing represent a potentially promising class of anti-cancer agents, currently progressing to clinical development. 

This Special Issue of IJMS intends to provide new research results to broaden our understanding of dysregulated RNA processing in disease and its effects on disease progression and treatment efficacy, as well as identification of new biomarkers, therapeutic targets and experimental medicines based on this knowledge. Novel insights that may contribute to more effective cancer treatment are of particular interest for this issue. Authors are invited to submit their original research and timely review articles.

Relevant topics include, but are not limited to: 

  • Identification of disease-associated patterns of dysregulated RNA processing
  • Detection of genetic alterations in cancer that affect RNA processing
  • RNA splicing isoforms as potential biomarkers and therapeutic targets
  • Structural and functional analysis of RNA modifying proteins
  • Discovery of drugs targeting RNA modifying proteins
  • Preclinical or clinical evaluation of spliceosome-targeting compounds
  • Strategies to modulate oncogenic RNA splicing events
  • Bioinformatic analysis methods to study dysregulated RNA processing
  • Identification of putative cancer neoantigens formed by aberrant RNA processing

Prof. Dr. Victor van Beusechem
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • RNA splicing
  • RNA editing
  • RNA methylation
  • (supra) spliceosome
  • antisense oligonucleotides
  • RNA interference
  • small molecules
  • cancer biomarkers
  • cancer therapy

Published Papers (2 papers)

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Research

14 pages, 5878 KiB  
Article
RNA Overwriting of Cellular mRNA by Cas13b-Directed RNA-Dependent RNA Polymerase of Influenza A Virus
by Shinzi Ogasawara and Sae Ebashi
Int. J. Mol. Sci. 2023, 24(12), 10000; https://doi.org/10.3390/ijms241210000 - 11 Jun 2023
Viewed by 1546
Abstract
Dysregulation of mRNA processing results in diseases such as cancer. Although RNA editing technologies attract attention as gene therapy for repairing aberrant mRNA, substantial sequence defects arising from mis-splicing cannot be corrected by existing techniques using adenosine deaminase acting on RNA (ADAR) due [...] Read more.
Dysregulation of mRNA processing results in diseases such as cancer. Although RNA editing technologies attract attention as gene therapy for repairing aberrant mRNA, substantial sequence defects arising from mis-splicing cannot be corrected by existing techniques using adenosine deaminase acting on RNA (ADAR) due to the limitation of adenosine-to-inosine point conversion. Here, we report an RNA editing technology called “RNA overwriting” that overwrites the sequence downstream of a designated site on the target RNA by utilizing the RNA-dependent RNA polymerase (RdRp) of the influenza A virus. To enable RNA overwriting within living cells, we developed a modified RdRp by introducing H357A and E361A mutations in the polymerase basic 2 of RdRp and fusing the C-terminus with catalytically inactive Cas13b (dCas13b). The modified RdRp knocked down 46% of the target mRNA and further overwrote 21% of the mRNA. RNA overwriting is a versatile editing technique that can perform various modifications, including addition, deletion, and mutation introduction, and thus allow for repair of the aberrant mRNA produced by dysregulation of mRNA processing, such as mis-splicing. Full article
(This article belongs to the Special Issue Targeting Dysregulated RNA Processing in Disease)
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8 pages, 874 KiB  
Communication
The Pattern of RNA Editing Changes in Pleural Mesothelioma upon Epithelial-Mesenchymal Transition
by Emanuela Felley-Bosco, Weihong Qi, Didier Jean, Clément Meiller and Hubert Rehrauer
Int. J. Mol. Sci. 2023, 24(3), 2874; https://doi.org/10.3390/ijms24032874 - 2 Feb 2023
Viewed by 1615
Abstract
Pleural mesothelioma (PM) is a cancer where epithelioid, biphasic and sarcomatoid histotypes are observed. Sarcomatoid PM is characterized by mesenchymal features. Multi-omics have been used to characterize the epithelial-to-mesenchymal (EMT) phenotype at the molecular level. We contribute to this effort by including the [...] Read more.
Pleural mesothelioma (PM) is a cancer where epithelioid, biphasic and sarcomatoid histotypes are observed. Sarcomatoid PM is characterized by mesenchymal features. Multi-omics have been used to characterize the epithelial-to-mesenchymal (EMT) phenotype at the molecular level. We contribute to this effort by including the analysis of RNA editing. We extracted samples with the highest vs. lowest Epithelial score from two PM cohorts and observed increased RNA editing in introns and decreased RNA editing in 3′UTR upon EMT. The same was observed in primary PM primary cultures stratified by transcriptomics analysis into two groups, one of them enriched with mesenchymal features. Our data demonstrate that, as has been observed in other cancer types, RNA editing associates to EMT phenotype in PM. Full article
(This article belongs to the Special Issue Targeting Dysregulated RNA Processing in Disease)
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