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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

Manuscript Submission Information

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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.

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Keywords

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

Published Papers (2 papers)

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Research

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26 pages, 5548 KiB

Open AccessArticle

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

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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, 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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10 pages, 981 KiB

Open AccessBrief 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 - 06 Dec 2023

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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 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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