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Non-coding RNA Biogenesis and Function 2021
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Non-coding RNA Biogenesis and Function 2021

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 (30 June 2022) | Viewed by 22716

Special Issue Editor

Dr. Mariangela Morlando

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Perugia, Via del Giochetto, 06123 Perugia, Italy
Interests: molecular biology; regulation of gene expression; noncoding RNA biogenesis and function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last few decades, we have witnessed extraordinary progress in the knowledge of how the noncoding part of the eukaryotic genome determines the organism’s complexity. In particular, higher eukaryote genomes produce different classes of regulatory noncoding RNAs (ncRNA), with examples including short RNA molecules of 22–35 nucleotides (nts), such as microRNAs and PIWI-interacting RNAs (piRNAs), as well as transcripts such as the long noncoding RNAs (lncRNAs), which generally refer to noncoding molecules longer than 200 nts, and the newly emerging class of circular RNAs (circRNAs). All these ncRNAs hold important regulatory roles in a wide range of biological processes, operating at any step throughout the genetic expression process, from transcription to RNA maturation and translation. However, the regulatory functions of many ncRNAs are not yet known, and this provides a rich environment for the development of new bioinformatic tools and experimental approaches for functional studies.

More importantly, the deregulation of ncRNAs has been associated with a variety of different diseases, and emerging studies suggest that they represent a new potential class of diagnostic and prognostic biomarkers.

The present Special Issue is aimed at collecting the latest advances and outstanding research investigating the biogenesis and function of different classes of ncRNAs and their possible involvement in disease pathogenesis. Original research and review manuscripts are welcome.

Dr. Mariangela Morlando
Guest Editor

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Keywords

  • Long noncoding RNAs (lncRNAs)
  • MicroRNAs
  • PIWI-interacting RNAs (piRNAs)
  • Circular RNAs (circRNAs)
  • RNA maturation and translation
  • Deregulation of ncRNAs
  • Disease pathogenesis
  • Biological processes
  • Non-coding RNA biogenesis

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Published Papers (5 papers)

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Research

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18 pages, 5662 KiB  
Article
Substrate Stiffness Drives Epithelial to Mesenchymal Transition and Proliferation through the NEAT1-Wnt/β-Catenin Pathway in Liver Cancer
by Xichao Xu, Yi Zhang, Xing Wang, Shun Li and Liling Tang
Int. J. Mol. Sci. 2021, 22(21), 12066; https://doi.org/10.3390/ijms222112066 - 8 Nov 2021
Cited by 33 | Viewed by 3887
Abstract
Background: Extracellular matrix (ECM)-derived mechanical stimuli regulate many cellular processes and phenotypes through mechanotransduction signaling pathways. Substrate stiffness changes cell phenotypes and promotes angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in tumors. Enhanced liver tissue matrix stiffness plays a crucial role in [...] Read more.
Background: Extracellular matrix (ECM)-derived mechanical stimuli regulate many cellular processes and phenotypes through mechanotransduction signaling pathways. Substrate stiffness changes cell phenotypes and promotes angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in tumors. Enhanced liver tissue matrix stiffness plays a crucial role in the tumorigenesis and malignant development of liver cancer and is associated with unfavorable survival outcomes. However, how liver cancer cells sense changes in ECM stiffness and the underlying molecular mechanisms are largely unknown. Methods: Seeding HepG2 cells on the micropillar gels, HepG2 cells were assessed for responsiveness to mechanotransduction using Western blot and immunofluorescence. Conclusions: We found that higher substrate stiffness dramatically enhanced malignant cell phenotypes and promoted G1/S transition in HepG2 cells. Furthermore, nuclear paraspeckle assembly transcript 1 (NEAT1) was identified as a matrix stiffness-responsive long non-coding RNA (lncRNA) regulating proliferation and EMT in response to increasing matrix stiffness during the progression of HepG2 cells towards liver cancer phenotypes. Higher matrix stiffness contributed to enhancing NEAT1 expression, which activated the WNT/β-catenin pathway. β-catenin translocates and enters the nucleus and the EMT transcription factor zinc finger E-box binding homeobox 1 (ZEB1) was upregulated to trigger EMT. Additionally, the proteins required for matrix stiffness-induced proliferation and resistance were strikingly upregulated in HepG2 cells. Therefore, our findings provide evidence that ECM-derived mechanical signals regulate cell proliferation and drive EMT through a NEAT1/WNT/β-catenin mechanotransduction pathway in the tumor microenvironment of liver cancer. Full article
(This article belongs to the Special Issue Non-coding RNA Biogenesis and Function 2021)
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14 pages, 1785 KiB  
Article
Investigation of LINC00493/SMIM26 Gene Suggests Its Dual Functioning at mRNA and Protein Level
by Daria Konina, Peter Sparber, Iuliia Viakhireva, Alexandra Filatova and Mikhail Skoblov
Int. J. Mol. Sci. 2021, 22(16), 8477; https://doi.org/10.3390/ijms22168477 - 6 Aug 2021
Cited by 3 | Viewed by 2841
Abstract
The amount of human long noncoding RNA (lncRNA) genes is comparable to protein-coding; however, only a small number of lncRNAs are functionally annotated. Previously, it was shown that lncRNAs can participate in many key cellular processes, including regulation of gene expression at transcriptional [...] Read more.
The amount of human long noncoding RNA (lncRNA) genes is comparable to protein-coding; however, only a small number of lncRNAs are functionally annotated. Previously, it was shown that lncRNAs can participate in many key cellular processes, including regulation of gene expression at transcriptional and post-transcriptional levels. The lncRNA genes can contain small open reading frames (sORFs), and recent studies demonstrated that some of the resulting short proteins could play an important biological role. In the present study, we investigate the widely expressed lncRNA LINC00493. We determine the structure of the LINC00493 transcript, its cell localization and influence on cell physiology. Our data demonstrate that LINC00493 has an influence on cell viability in a cell-type-specific manner. Furthermore, it was recently shown that LINC00493 has a sORF that is translated into small protein SMIM26. The results of our knockdown and overexpression experiments suggest that both LINC00493/SMIM26 transcript and protein affect cell viability, but in the opposite manner. Full article
(This article belongs to the Special Issue Non-coding RNA Biogenesis and Function 2021)
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19 pages, 2994 KiB  
Article
m5U54 tRNA Hypomodification by Lack of TRMT2A Drives the Generation of tRNA-Derived Small RNAs
by Marisa Pereira, Diana R. Ribeiro, Miguel M. Pinheiro, Margarida Ferreira, Stefanie Kellner and Ana R. Soares
Int. J. Mol. Sci. 2021, 22(6), 2941; https://doi.org/10.3390/ijms22062941 - 14 Mar 2021
Cited by 36 | Viewed by 7883
Abstract
Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation [...] Read more.
Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification and tsRNA formation. More specifically, m5U54 hypomodification is followed by overexpression of the ribonuclease angiogenin (ANG) that cleaves tRNAs near the anticodon, resulting in accumulation of 5′tRNA-derived stress-induced RNAs (5′tiRNAs), namely 5′tiRNA-GlyGCC and 5′tiRNA-GluCTC, among others. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tiRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tiRNA formation in mammalian cells. These results establish a link between tRNA hypomethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark. Full article
(This article belongs to the Special Issue Non-coding RNA Biogenesis and Function 2021)
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Review

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27 pages, 1163 KiB  
Review
Non-Coding RNAs in Regulating Plaque Progression and Remodeling of Extracellular Matrix in Atherosclerosis
by Drishtant Singh, Vikrant Rai and Devendra K. Agrawal
Int. J. Mol. Sci. 2022, 23(22), 13731; https://doi.org/10.3390/ijms232213731 - 8 Nov 2022
Cited by 13 | Viewed by 2869
Abstract
Non-coding RNAs (ncRNAs) regulate cell proliferation, migration, differentiation, inflammation, metabolism of clinically important biomolecules, and other cellular processes. They do not encode proteins but are involved in the regulatory network of various proteins that are directly related to the pathogenesis of diseases. Little [...] Read more.
Non-coding RNAs (ncRNAs) regulate cell proliferation, migration, differentiation, inflammation, metabolism of clinically important biomolecules, and other cellular processes. They do not encode proteins but are involved in the regulatory network of various proteins that are directly related to the pathogenesis of diseases. Little is known about the ncRNA-associated mechanisms of atherosclerosis and related cardiovascular disorders. Remodeling of the extracellular matrix (ECM) is critical in the pathogenesis of atherosclerosis and related disorders; however, its regulatory proteins are the potential subjects to explore with special emphasis on epigenetic regulatory components. The activity of regulatory proteins involved in ECM remodeling is regulated by various ncRNA molecules, as evident from recent research. Thus, it is important to critically evaluate the existing literature to enhance the understanding of nc-RNAs-regulated molecular mechanisms regulating ECM components, remodeling, and progression of atherosclerosis. This is crucial since deregulated ECM remodeling contributes to atherosclerosis. Thus, an in-depth understanding of ncRNA-associated ECM remodeling may identify novel targets for the treatment of atherosclerosis and other cardiovascular diseases. Full article
(This article belongs to the Special Issue Non-coding RNA Biogenesis and Function 2021)
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25 pages, 1935 KiB  
Review
Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs
by Eleonora A. Braga, Marina V. Fridman, Alexey M. Burdennyy, Elena A. Filippova, Vitaly I. Loginov, Irina V. Pronina, Alexey A. Dmitriev and Nikolay E. Kushlinskii
Int. J. Mol. Sci. 2022, 23(21), 13620; https://doi.org/10.3390/ijms232113620 - 7 Nov 2022
Cited by 10 | Viewed by 4280
Abstract
A decrease in the miR-124 expression was observed in various epithelial cancers. Like a classical suppressor, miR-124 can inhibit the translation of multiple oncogenic proteins. Epigenetic mechanisms play a significant role in the regulation of miR-124 expression and involve hypermethylation of the MIR-124-1/-2/-3 [...] Read more.
A decrease in the miR-124 expression was observed in various epithelial cancers. Like a classical suppressor, miR-124 can inhibit the translation of multiple oncogenic proteins. Epigenetic mechanisms play a significant role in the regulation of miR-124 expression and involve hypermethylation of the MIR-124-1/-2/-3 genes and the effects of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) according to the model of competing endogenous RNAs (ceRNAs). More than 40 interactomes (lncRNA/miR-124/mRNA) based on competition between lncRNAs and mRNAs for miR-124 binding have been identified in various epithelial cancers. LncRNAs MALAT1, NEAT1, HOXA11-AS, and XIST are the most represented in these axes. Fourteen axes (e.g., SND1-IT1/miR-124/COL4A1) are involved in EMT and/or metastasis. Moreover, eight axes (e.g., OIP5-AS1/miR-124-5p/IDH2) are involved in key pathways, such as Wnt/b-catenin, E2F1, TGF-β, SMAD, ERK/MAPK, HIF-1α, Notch, PI3K/Akt signaling, and cancer cell stemness. Additionally, 15 axes impaired patient survival and three axes reduced chemo- or radiosensitivity. To date, 14 cases of miR-124 regulation by circRNAs have been identified. Half of them involve circHIPK3, which belongs to the exonic ecircRNAs and stimulates cell proliferation, EMT, autophagy, angiogenesis, and multidrug resistance. Thus, miR-124 and its interacting partners may be considered promising targets for cancer therapy. Full article
(This article belongs to the Special Issue Non-coding RNA Biogenesis and Function 2021)
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