Impact of 3'UTR Variants on mRNA Stability

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 1452

Special Issue Editors


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Experimental Nephrology Lab, Institut d’Investigació Biomèdica de Bellvitge-IDIBELL, C/ Feixa Llarga s/n, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
Interests: molecular medicine; predictive medicine; personalized medicine; inflammation; ncRNAs
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Special Issue Information

Dear Colleagues,

Recent years have seen a huge increase in the number of works describing the nature and function of newly described regulatory RNAs. This knowledge has allowed for the delineation of complex regulatory networks that relate mRNAs’ stability to the expression of microRNAs (miRNAs) and lncRNAs (as miRNA sponges).

Additionally, a number of authors have recently described a new functional feature of mRNAs that directly impacts the establishment of these RNA regulatory networks, i.e., the dynamic expression of different 3’UTR isoforms to regulate the accession of miRNAs to their target mRNA sequences.

In this Special Issue we are interested in the mechanisms that generate 3’UTR diversity in normal and disease cells (such as alternative polyadenylation, alternative splicing, or the exonization of repetitive elements), in addition to their impact on mRNA function. Furthermore, we are also especially interested in the use of alternative 3’UTRs for the stabilization of mRNA vaccines.

We are also willing to receive originals on technical developments that have facilitated the generation as well as analysis of transcriptonic information of 3’UTR variants and their impact on mRNA stability and function:

  • Development of software to extract variant 3’UTR data from RNA.seq/single-cell RNA.seq runs;
  • Generation of databases of variant 3’UTRs in human diseases;
  • New experimental techniques for the high-throughput targeting of mRNA–miRNA as well as miRNA–lncRNA interactions;
  • Software for modeling mRNA–miRNA–lncRNA networks, including alternative 3’UTRs

Dr. Estanislao Navarro
Dr. Miguel Hueso
Guest Editors

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Published Papers (1 paper)

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Research

17 pages, 2761 KiB  
Article
Generation of Transcript Length Variants and Reprogramming of mRNA Splicing During Atherosclerosis Progression in ApoE-Deficient Mice
by Miguel Hueso, Adrián Mallén and Estanis Navarro
Biomedicines 2024, 12(12), 2703; https://doi.org/10.3390/biomedicines12122703 - 26 Nov 2024
Viewed by 914
Abstract
Background. Variant 3′UTRs provide mRNAs with different binding sites for miRNAs or RNA-binding proteins (RBPs) allowing the establishment of new regulatory environments. Regulation of 3′UTR length impacts on the control of gene expression by regulating accessibility of miRNAs or RBPs to homologous sequences [...] Read more.
Background. Variant 3′UTRs provide mRNAs with different binding sites for miRNAs or RNA-binding proteins (RBPs) allowing the establishment of new regulatory environments. Regulation of 3′UTR length impacts on the control of gene expression by regulating accessibility of miRNAs or RBPs to homologous sequences in mRNAs. Objective. Studying the dynamics of mRNA length variations in atherosclerosis (ATS) progression and reversion in ApoE-deficient mice exposed to a high-fat diet and treated with an αCD40-specific siRNA or with a sequence-scrambled siRNA as control. Methods. We gathered microarray mRNA expression data from the aortas of mice after 2 or 16 weeks of treatments, and used these data in a Bioinformatics analysis. Results. Here, we report the lengthening of the 5′UTR/3′UTRs and the shortening of the CDS in downregulated mRNAs during ATS progression. Furthermore, treatment with the αCD40-specific siRNA resulted in the partial reversion of the 3′UTR lengthening. Exon analysis showed that these length variations were actually due to changes in the number of exons embedded in mRNAs, and the further examination of transcripts co-expressed at weeks 2 and 16 in mice treated with the control siRNA revealed a process of mRNA isoform switching in which transcript variants differed in the patterns of alternative splicing or activated latent/cryptic splice sites. Conclusion. We document length variations in the 5′UTR/3′UTR and CDS of mRNAs downregulated during atherosclerosis progression and suggest a role for mRNA splicing reprogramming and transcript isoform switching in the generation of disease-related mRNA sequence diversity and variability. Full article
(This article belongs to the Special Issue Impact of 3'UTR Variants on mRNA Stability)
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