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Recent Progress in Molecular Biology of RNA 2.0

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

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 10559

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Special Issue Information

Dear Colleagues,

When it was demonstrated in 1961 that the genetic information contained in DNA was provided into the locus to be translated into protein via an intermediary, the messenger RNA, RNA turned out to be the key in genome expression. RNA implication in cell biology rapidly extended to non-coding RNAs, whose function in translational machinery and splicing was shown as essential. A major milestone demonstrating the importance of RNA appeared in the beginning of the 21st century with the discovery that only 2% of the human genome codes proteins while 75% is transcribed, revealing the existence of numerous non-coding RNAs. Then, several families of non-coding RNAs were discovered, including microRNAs, long non-coding RNAs, circular RNAs, etc., which are fully involved in the epigenetics landscape. All this fundamental knowledge on RNA associated with the strong technological advances of these last few years provided by cutting-edge technologies in molecular biology led to biotechnological and medical applications of RNA. Technologies such as RNA interference and genome edition with the CRISPR Cas9, based on guide RNAs, have provided powerful tools to control gene expression. More recently, the mRNA vaccine against SARS-COV-2 has opened the way toward a new generation of RNA-based therapeutics. This Special Issue aims to update the state of art in this fascinating RNA world, on both basic and applied research aspects.

Potential topics include (but are not limited to):

  • Molecular mechanisms involving RNA
  • mRNA translational control
  • RNA maturation and metabolism
  • Non-coding RNAs
  • Circular RNAs
  • RNA–protein complexes
  • RNA in biotechnology
  • RNA and diseases
  • RNA-based therapeutics

Dr. Anne-Catherine Prats
Guest Editor

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Keywords

  • mRNA
  • ncRNA
  • circRNA
  • translation
  • RNA-binding proteins
  • genome edition
  • diseases
  • therapeutics

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Published Papers (7 papers)

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Research

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19 pages, 3172 KiB  
Article
Npac Regulates Pre-mRNA Splicing in Mouse Embryonic Stem Cells
by Yiwei Qian, Ying Ye, Wensheng Zhang and Qiang Wu
Int. J. Mol. Sci. 2024, 25(19), 10396; https://doi.org/10.3390/ijms251910396 - 27 Sep 2024
Viewed by 1159
Abstract
As a reader of tri-methylated lysine 36 on histone H3 (H3K36me3), Npac has been shown to have a significant role in gene transcription elongation. However, its potential implication in RNA splicing remains unknown. Here, we characterized the phenotypes of Npac knockout in mES [...] Read more.
As a reader of tri-methylated lysine 36 on histone H3 (H3K36me3), Npac has been shown to have a significant role in gene transcription elongation. However, its potential implication in RNA splicing remains unknown. Here, we characterized the phenotypes of Npac knockout in mES cells. We discovered that loss of Npac disrupts pluripotency and identity in mESCs. We also found that Npac is associated with many cellular activities, including cell proliferation, differentiation, and transcription regulation. Notably, we uncovered that Npac is associated with RNA splicing machinery. Furthermore, we found that Npac regulates alternative splicing through its interaction with the splicing factors, including Srsf1. Our research thus highlights the important role of Npac in maintaining ESC identity through the regulation of pre-mRNA splicing. Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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14 pages, 6176 KiB  
Article
Poly (I:C)-Induced microRNA-30b-5p Negatively Regulates the JAK/STAT Signaling Pathway to Mediate the Antiviral Immune Response in Silver Carp (Hypophthalmichthys molitrix) via Targeting CRFB5
by Meng Liu, Huan Tang, Kun Gao, Xiqing Zhang, Zhenhua Ma, Yunna Jia, Zihan Yang, Muhammad Inam, Yunhang Gao, Guiqin Wang and Xiaofeng Shan
Int. J. Mol. Sci. 2024, 25(11), 5712; https://doi.org/10.3390/ijms25115712 - 24 May 2024
Cited by 2 | Viewed by 1148
Abstract
In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, [...] Read more.
In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response. Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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26 pages, 5548 KiB  
Article
Mitochondrial Ribosomal Protein MRPS15 Is a Component of Cytosolic Ribosomes and Regulates Translation in Stressed Cardiomyocytes
by Florian David, Emilie Roussel, Carine Froment, Tangra Draia-Nicolau, Françoise Pujol, Odile Burlet-Schiltz, Anthony K. Henras, Eric Lacazette, Florent Morfoisse, Florence Tatin, Jean-Jacques Diaz, Frédéric Catez, Barbara Garmy-Susini and Anne-Catherine Prats
Int. J. Mol. Sci. 2024, 25(6), 3250; https://doi.org/10.3390/ijms25063250 - 13 Mar 2024
Viewed by 2479
Abstract
Regulation of mRNA translation is a crucial step in controlling gene expression in stressed cells, impacting many pathologies, including heart ischemia. In recent years, ribosome heterogeneity has emerged as a key control mechanism driving the translation of subsets of mRNAs. In this study, [...] Read more.
Regulation of mRNA translation is a crucial step in controlling gene expression in stressed cells, impacting many pathologies, including heart ischemia. In recent years, ribosome heterogeneity has emerged as a key control mechanism driving the translation of subsets of mRNAs. In this study, we investigated variations in ribosome composition in human cardiomyocytes subjected to endoplasmic reticulum stress induced by tunicamycin treatment. Our findings demonstrate that this stress inhibits global translation in cardiomyocytes while activating internal ribosome entry site (IRES)-dependent translation. Analysis of translating ribosome composition in stressed and unstressed cardiomyocytes was conducted using mass spectrometry. We observed no significant changes in ribosomal protein composition, but several mitochondrial ribosomal proteins (MRPs) were identified in cytosolic polysomes, showing drastic variations between stressed and unstressed cells. The most notable increase in polysomes of stressed cells was observed in MRPS15. Its interaction with ribosomal proteins was confirmed by proximity ligation assay (PLA) and immunoprecipitation, suggesting its intrinsic role as a ribosomal component during stress. Knock-down or overexpression experiments of MRPS15 revealed its role as an activator of IRES-dependent translation. Furthermore, polysome profiling after immunoprecipitation with anti-MRPS15 antibody revealed that the “MRPS15 ribosome” is specialized in translating mRNAs involved in the unfolded protein response. Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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Review

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25 pages, 3476 KiB  
Review
Structural Features of 5′ Untranslated Region in Translational Control of Eukaryotes
by Elizaveta Razumova, Aleksandr Makariuk, Olga Dontsova, Nikita Shepelev and Maria Rubtsova
Int. J. Mol. Sci. 2025, 26(5), 1979; https://doi.org/10.3390/ijms26051979 - 25 Feb 2025
Viewed by 1022
Abstract
Gene expression is a complex process regulated at multiple levels in eukaryotic cells. Translation frequently represents a pivotal step in the control of gene expression. Among the stages of translation, initiation is particularly important, as it governs ribosome recruitment and the efficiency of [...] Read more.
Gene expression is a complex process regulated at multiple levels in eukaryotic cells. Translation frequently represents a pivotal step in the control of gene expression. Among the stages of translation, initiation is particularly important, as it governs ribosome recruitment and the efficiency of protein synthesis. The 5′ untranslated region (5′ UTR) of mRNA plays a key role in this process, often exhibiting a complicated and structured landscape. Numerous eukaryotic mRNAs possess long 5′ UTRs that contain diverse regulatory elements, including RNA secondary structures, specific nucleotide motifs, and chemical modifications. These structural features can independently modulate translation through their intrinsic properties or by serving as platforms for trans-acting factors such as RNA-binding proteins. The dynamic nature of 5′ UTR elements allows cells to fine-tune translation in response to environmental and cellular signals. Understanding these mechanisms is not only fundamental to molecular biology but also holds significant biomedical potential. Insights into 5′ UTR-mediated regulation could drive advancements in synthetic biology and mRNA-based targeted therapies. This review outlines the current knowledge of the structural elements of the 5′ UTR, the interplay between them, and their combined functional impact on translation. Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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22 pages, 4875 KiB  
Review
CRISPR/Cas9 Genome Editing in the Diamondback Moth: Current Progress, Challenges, and Prospects
by Muhammad Asad, Yanpeng Chang, Jianying Liao and Guang Yang
Int. J. Mol. Sci. 2025, 26(4), 1515; https://doi.org/10.3390/ijms26041515 - 11 Feb 2025
Viewed by 775
Abstract
The development of site-specific genome-editing tools like CRISPR (clustered regularly interspaced short palindromic repeat) and its associated protein, Cas9, is revolutionizing genetic engineering with its highly efficient mechanism, offering the potential for effective pest management. Recently, CRISPR/Cas9 gene-editing has been extensively utilized in [...] Read more.
The development of site-specific genome-editing tools like CRISPR (clustered regularly interspaced short palindromic repeat) and its associated protein, Cas9, is revolutionizing genetic engineering with its highly efficient mechanism, offering the potential for effective pest management. Recently, CRISPR/Cas9 gene-editing has been extensively utilized in the management of the diamondback moth, Plutella xylostella (L.), a highly destructive pest of vegetable crops, for different purposes, such as gene function analysis and genetic control. However, the progress related to this gene-editing tool in P. xylostella has not yet been summarized. This review highlights the progress and applications of CRISPR/Cas9 in uncovering the genes critical for development, reproduction, and insecticide resistance in P. xylostella. Moreover, the progress related to the CRISPR/Cas9 gene drive for population suppression and modifications has also been discussed. In addition to the significant progress made, challenges such as low germline editing efficiency and limited homology-directed repair remain obstacles to its widespread application. To address these limitations, we have discussed the different strategies that are anticipated to improve the efficiency of CRISPR/Cas9, paving the way to it becoming a pivotal tool in sustainable pest management. Therefore, the present review will help researchers in the future enhance the efficiency of the CRISPR/Cas9 system and use it to manage the diamondback moth. Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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37 pages, 3068 KiB  
Review
Circular RNAs in Cell Cycle Regulation of Cancers
by Pannathon Thamjamrassri and Chaiyaboot Ariyachet
Int. J. Mol. Sci. 2024, 25(11), 6094; https://doi.org/10.3390/ijms25116094 - 31 May 2024
Cited by 3 | Viewed by 1599
Abstract
Cancer has been one of the most problematic health issues globally. Typically, all cancers share a common characteristic or cancer hallmark, such as sustaining cell proliferation, evading growth suppressors, and enabling replicative immortality. Indeed, cell cycle regulation in cancer is often found to [...] Read more.
Cancer has been one of the most problematic health issues globally. Typically, all cancers share a common characteristic or cancer hallmark, such as sustaining cell proliferation, evading growth suppressors, and enabling replicative immortality. Indeed, cell cycle regulation in cancer is often found to be dysregulated, leading to an increase in aggressiveness. These dysregulations are partly due to the aberrant cellular signaling pathway. In recent years, circular RNAs (circRNAs) have been widely studied and classified as one of the regulators in various cancers. Numerous studies have reported that circRNAs antagonize or promote cancer progression through the modulation of cell cycle regulators or their associated signaling pathways, directly or indirectly. Mostly, circRNAs are known to act as microRNA (miRNA) sponges. However, they also hold additional mechanisms for regulating cellular activity, including protein binding, RNA-binding protein (RBP) recruitment, and protein translation. This review will discuss the current knowledge of how circRNAs regulate cell cycle-related proteins through the abovementioned mechanisms in different cancers. Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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Other

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10 pages, 981 KiB  
Brief Report
Quantitative Investigation of FAD2 Cosuppression Reveals RDR6-Dependent and RDR6-Independent Gene Silencing Pathways
by Yangyang Chen, Hangkai Ku, Yingdong Zhao, Chang Du and Meng Zhang
Int. J. Mol. Sci. 2023, 24(24), 17165; https://doi.org/10.3390/ijms242417165 - 6 Dec 2023
Viewed by 1483
Abstract
The frequency and extent of transgene-mediated cosuppression varies substantially among plant genes. However, the underlying mechanisms leading to strong cosuppression have received little attention. In previous studies, we showed that the expression of FAD2 in the seeds of Arabidopsis results in strong RDR6-mediated [...] Read more.
The frequency and extent of transgene-mediated cosuppression varies substantially among plant genes. However, the underlying mechanisms leading to strong cosuppression have received little attention. In previous studies, we showed that the expression of FAD2 in the seeds of Arabidopsis results in strong RDR6-mediated cosuppression, where both endogenous and transgenic FAD2 were silenced. Here, the FAD2 strong cosuppression system was quantitatively investigated to identify the genetic factors by the expression of FAD2 in their mutants. The involvement of DCL2, DCL4, AGO1, and EIN5 was first confirmed in FAD2 cosuppression. SKI2, a remover of 3′ end aberrant RNAs, was newly identified as being involved in the cosuppression, while DCL3 was identified as antagonistic to DCL2 and DCL3. FAD2 cosuppression was markedly reduced in dcl2, dcl4, and ago1. The existence of an RDR6-independent cosuppression was revealed for the first time, which was demonstrated by weak gene silencing in rdr6 ein5 ski2. Further investigation of FAD2 cosuppression may unveil unknown genetic factor(s). Full article
(This article belongs to the Special Issue Recent Progress in Molecular Biology of RNA 2.0)
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