Special Issue "Post-transcriptional Regulation through Long Non-coding RNAs (lncRNAs)"

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (31 December 2020).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Michael R. Ladomery
E-Mail Website
Guest Editor
Faculty of Health and Applied Sciences, University of the West of England, Bristol BS16 1QY, UK
Interests: RNA biology; RNA binding proteins; alternative splicing; splice factors; splice factor kinases; mRNA translation; microRNAs
Special Issues and Collections in MDPI journals
Dr. Giuseppina Pisignano
E-Mail Website
Co-Guest Editor
Department of Biology and Biochemistry, University of Bath, Bath, UK
Interests: Epigenetics; RNA biology; lncRNAs; RNA structure; microRNA; non-coding variants; chromatin conformation; gene expression regulation; CRISPR/Cas9 technology

Special Issue Information

Dear Colleagues,

It is increasingly apparent that noncoding RNAs play a major role in gene regulation. In particular, it is now undisputed that microRNAs are involved in several key developmental and pathological processes. But it is also clear that other types of regulatory noncoding RNAs exist; in particular, long noncoding RNAs (lncRNAs). These lncRNAs exert their biological functions through a bewildering array of mechanisms, including a direct effect on epigenetic regulation through the modification of chromatin, as well as the direct modulation of protein activity and localization. However, it is also clear that lncRNAs work post-transcriptionally. They are involved in the regulation of expression and activity of other ncRNAs including microRNAs. They contribute to the regulation of alternative splicing, an increasingly key process in the regulation of gene expression. LncRNAs are also involved in the regulation of RNA editing, export, translation and stability. The focus of this Special Issue is on post-transcriptional regulation of gene expression by lncRNAs. A full understanding of lncRNA biology needs to include a better understanding of how they contribute to gene regulation post-transcriptionally in both normal development and disease.

Dr. Michael R. Ladomery
Guest Editor

Dr. Giuseppina Pisignano
Co-Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). 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 biology
  • Long noncoding RNAs (lncRNAs)
  • Short noncoding RNAs, microRNAs
  • Post-transcriptional regulation
  • Alternative splicing
  • RNA editing, RNA export, mRNA translation and stability
  • RNA binding proteins

Published Papers (9 papers)

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Editorial

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Editorial
Post-Transcriptional Regulation through Long Non-Coding RNAs (lncRNAs)
Non-Coding RNA 2021, 7(2), 29; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7020029 - 29 Apr 2021
Cited by 1 | Viewed by 1810
Abstract
The discovery of thousands of non-coding RNAs (ncRNAs) pervasively transcribed from the eukaryotic genome has revolutionized the “central dogma” of biology and shifted the attention on the role of RNAs as regulatory molecules, more than simply traditional mediators of genomic information [...] Full article

Research

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Article
Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation
Non-Coding RNA 2021, 7(2), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7020026 - 16 Apr 2021
Cited by 2 | Viewed by 2183
Abstract
Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play [...] Read more.
Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their availability is tightly regulated by RNA competing mechanisms often mediated by long noncoding RNAs (lncRNAs). In our paper, we simulated the response to growth adverse condition by bimiralisib, a dual PI3K/mTOR inhibitor, in diffuse large B cell lymphoma cell lines, and we studied post-transcriptional regulation by the differential analysis of exonic and intronic RNA expression. In particular, we observed the upregulation of a lncRNA, lncTNK2-2:1, which correlated with the stabilization of transcripts involved in the regulation of translation and DNA damage after bimiralisib treatment. We identified miR-21-3p as miRNA likely sponged by lncTNK2-2:1, with consequent stabilization of the mRNA of p53, which is a master regulator of cell growth in response to DNA damage. Full article
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Review

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Review
Epigenetic Regulation of Alternative Splicing: How LncRNAs Tailor the Message
Non-Coding RNA 2021, 7(1), 21; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010021 - 11 Mar 2021
Cited by 1 | Viewed by 2440
Abstract
Alternative splicing is a highly fine-tuned regulated process and one of the main drivers of proteomic diversity across eukaryotes. The vast majority of human multi-exon genes is alternatively spliced in a cell type- and tissue-specific manner, and defects in alternative splicing can dramatically [...] Read more.
Alternative splicing is a highly fine-tuned regulated process and one of the main drivers of proteomic diversity across eukaryotes. The vast majority of human multi-exon genes is alternatively spliced in a cell type- and tissue-specific manner, and defects in alternative splicing can dramatically alter RNA and protein functions and lead to disease. The eukaryotic genome is also intensively transcribed into long and short non-coding RNAs which account for up to 90% of the entire transcriptome. Over the years, lncRNAs have received considerable attention as important players in the regulation of cellular processes including alternative splicing. In this review, we focus on recent discoveries that show how lncRNAs contribute significantly to the regulation of alternative splicing and explore how they are able to shape the expression of a diverse set of splice isoforms through several mechanisms. With the increasing number of lncRNAs being discovered and characterized, the contribution of lncRNAs to the regulation of alternative splicing is likely to grow significantly. Full article
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Review
Approaches to Identify and Characterise the Post-Transcriptional Roles of lncRNAs in Cancer
Non-Coding RNA 2021, 7(1), 19; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010019 - 09 Mar 2021
Cited by 1 | Viewed by 2257
Abstract
It is becoming increasingly evident that the non-coding genome and transcriptome exert great influence over their coding counterparts through complex molecular interactions. Among non-coding RNAs (ncRNA), long non-coding RNAs (lncRNAs) in particular present increased potential to participate in dysregulation of post-transcriptional processes through [...] Read more.
It is becoming increasingly evident that the non-coding genome and transcriptome exert great influence over their coding counterparts through complex molecular interactions. Among non-coding RNAs (ncRNA), long non-coding RNAs (lncRNAs) in particular present increased potential to participate in dysregulation of post-transcriptional processes through both RNA and protein interactions. Since such processes can play key roles in contributing to cancer progression, it is desirable to continue expanding the search for lncRNAs impacting cancer through post-transcriptional mechanisms. The sheer diversity of mechanisms requires diverse resources and methods that have been developed and refined over the past decade. We provide an overview of computational resources as well as proven low-to-high throughput techniques to enable identification and characterisation of lncRNAs in their complex interactive contexts. As more cancer research strategies evolve to explore the non-coding genome and transcriptome, we anticipate this will provide a valuable primer and perspective of how these technologies have matured and will continue to evolve to assist researchers in elucidating post-transcriptional roles of lncRNAs in cancer. Full article
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Review
The Role of LncRNAs in Translation
Non-Coding RNA 2021, 7(1), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010016 - 20 Feb 2021
Cited by 5 | Viewed by 2131
Abstract
Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular [...] Read more.
Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters. Full article
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Review
Endogenous Double-Stranded RNA
Non-Coding RNA 2021, 7(1), 15; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010015 - 19 Feb 2021
Cited by 4 | Viewed by 2415
Abstract
The birth of long non-coding RNAs (lncRNAs) is closely associated with the presence and activation of repetitive elements in the genome. The transcription of endogenous retroviruses as well as long and short interspersed elements is not only essential for evolving lncRNAs but is [...] Read more.
The birth of long non-coding RNAs (lncRNAs) is closely associated with the presence and activation of repetitive elements in the genome. The transcription of endogenous retroviruses as well as long and short interspersed elements is not only essential for evolving lncRNAs but is also a significant source of double-stranded RNA (dsRNA). From an lncRNA-centric point of view, the latter is a minor source of bother in the context of the entire cell; however, dsRNA is an essential threat. A viral infection is associated with cytoplasmic dsRNA, and endogenous RNA hybrids only differ from viral dsRNA by the 5′ cap structure. Hence, a multi-layered defense network is in place to protect cells from viral infections but tolerates endogenous dsRNA structures. A first line of defense is established with compartmentalization; whereas endogenous dsRNA is found predominantly confined to the nucleus and the mitochondria, exogenous dsRNA reaches the cytoplasm. Here, various sensor proteins recognize features of dsRNA including the 5′ phosphate group of viral RNAs or hybrids with a particular length but not specific nucleotide sequences. The sensors trigger cellular stress pathways and innate immunity via interferon signaling but also induce apoptosis via caspase activation. Because of its central role in viral recognition and immune activation, dsRNA sensing is implicated in autoimmune diseases and used to treat cancer. Full article
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Review
Plant Long Noncoding RNAs: New Players in the Field of Post-Transcriptional Regulations
Non-Coding RNA 2021, 7(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010012 - 17 Feb 2021
Cited by 2 | Viewed by 2948
Abstract
The first reference to the “C-value paradox” reported an apparent imbalance between organismal genome size and morphological complexity. Since then, next-generation sequencing has revolutionized genomic research and revealed that eukaryotic transcriptomes contain a large fraction of non-protein-coding components. Eukaryotic genomes are pervasively transcribed [...] Read more.
The first reference to the “C-value paradox” reported an apparent imbalance between organismal genome size and morphological complexity. Since then, next-generation sequencing has revolutionized genomic research and revealed that eukaryotic transcriptomes contain a large fraction of non-protein-coding components. Eukaryotic genomes are pervasively transcribed and noncoding regions give rise to a plethora of noncoding RNAs with undeniable biological functions. Among them, long noncoding RNAs (lncRNAs) seem to represent a new layer of gene expression regulation, participating in a wide range of molecular mechanisms at the transcriptional and post-transcriptional levels. In addition to their role in epigenetic regulation, plant lncRNAs have been associated with the degradation of complementary RNAs, the regulation of alternative splicing, protein sub-cellular localization, the promotion of translation and protein post-translational modifications. In this review, we report and integrate numerous and complex mechanisms through which long noncoding transcripts regulate post-transcriptional gene expression in plants. Full article
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Review
The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization
Non-Coding RNA 2021, 7(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010003 - 05 Jan 2021
Cited by 3 | Viewed by 2487
Abstract
mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide [...] Read more.
mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability. Full article
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Review
Long Non-Coding RNA-Ribonucleoprotein Networks in the Post-Transcriptional Control of Gene Expression
Non-Coding RNA 2020, 6(3), 40; https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna6030040 - 17 Sep 2020
Cited by 5 | Viewed by 2334
Abstract
Although mammals possess roughly the same number of protein-coding genes as worms, it is evident that the non-coding transcriptome content has become far broader and more sophisticated during evolution. Indeed, the vital regulatory importance of both short and long non-coding RNAs (lncRNAs) has [...] Read more.
Although mammals possess roughly the same number of protein-coding genes as worms, it is evident that the non-coding transcriptome content has become far broader and more sophisticated during evolution. Indeed, the vital regulatory importance of both short and long non-coding RNAs (lncRNAs) has been demonstrated during the last two decades. RNA binding proteins (RBPs) represent approximately 7.5% of all proteins and regulate the fate and function of a huge number of transcripts thus contributing to ensure cellular homeostasis. Transcriptomic and proteomic studies revealed that RBP-based complexes often include lncRNAs. This review will describe examples of how lncRNA-RBP networks can virtually control all the post-transcriptional events in the cell. Full article
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