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Non-Coding RNA Biogenesis and Function 2020
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Non-Coding RNA Biogenesis and Function 2020

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 November 2020) | Viewed by 29158

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 an extraordinary progress in the knowledge of how the non-coding part of the eukaryotic genome determines the organism’s complexity. Higher eukaryote genomes produce different classes of regulatory non-coding 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 are generally referred to as 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 bioinformatics tools and experimental approaches for functional studies.

More importantly, 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.

Thus, this new Special Issue aims to collect the latest advances and outstanding research investigating 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 (7 papers)

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Research

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21 pages, 31022 KiB  
Article
Profiling and Functional Analysis of Long Noncoding RNAs and mRNAs during Porcine Skeletal Muscle Development
by Ya Tan, Mailin Gan, Linyuan Shen, Liang Li, Yuan Fan, Ying Chen, Lei Chen, Lili Niu, Ye Zhao, Anan Jiang, Dongmei Jiang, Shunhua Zhang and Li Zhu
Int. J. Mol. Sci. 2021, 22(2), 503; https://doi.org/10.3390/ijms22020503 - 6 Jan 2021
Cited by 7 | Viewed by 2882
Abstract
Gene transcripts or mRNAs and long noncoding RNAs (lncRNAs) are differentially expressed during porcine skeletal muscle development. However, only a few studies have been conducted on skeletal muscle transcriptome in pigs based on timepoints according to the growth curve for porcine. Here, we [...] Read more.
Gene transcripts or mRNAs and long noncoding RNAs (lncRNAs) are differentially expressed during porcine skeletal muscle development. However, only a few studies have been conducted on skeletal muscle transcriptome in pigs based on timepoints according to the growth curve for porcine. Here, we investigated gene expression in Qingyu pigs at three different growth stages: the inflection point with the maximum growth rate (MGI), the inflection point of the gradually increasing stage to the rapidly increasing stage (GRI), and the inflection point of the rapidly increasing stage to the slowly increasing stage (RSI). Subsequently, we explored gene expression profiles during muscle development at the MGI, GRI and RSI stages by Ribo-Zero RNA sequencing. Qingyu pigs reached the MGI, GRI and RSI stages at 156.40, 23.82 and 288.97 days of age with 51.73, 3.14 and 107.03 kg body weight, respectively. A total of 14,530 mRNAs and 11,970 lncRNAs were identified at the three stages, and 645, 323 differentially expressed genes (DEGs) and 696, 760 differentially expressed lncRNAs (DELs) were identified in the GRI vs. MGI, and RSI vs. MGI, comparisons. Functional enrichment analysis revealed that genes involved in immune system development and energy metabolism (mainly relate to amino acid, carbohydrate and lipid) were enriched at the GRI and MGI stages, respectively, whereas genes involved in lipid metabolism were enriched at the RSI stage. We further characterized G1430, an abundant lncRNA. The full-length sequence (316 nt) of lncRNA G1430 was determined by rapid amplification of cDNA ends (RACE). Subcellular distribution analysis by quantitative real-time PCR (qRT-PCR) revealed that G1430 is a cytoplasmic lncRNA. Binding site prediction and dual luciferase assay showed that lncRNA G1430 directly binds to microRNA 133a (miR-133a). Our findings provide the basis for further investigation of the regulatory mechanisms and molecular genetics of muscle development in pigs. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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23 pages, 3659 KiB  
Article
Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries
by Ilmatar Rooda, Mohammad Mehedi Hasan, Kristine Roos, Janeli Viil, Aneta Andronowska, Olli-Pekka Smolander, Ülle Jaakma, Andres Salumets, Alireza Fazeli and Agne Velthut-Meikas
Int. J. Mol. Sci. 2020, 21(24), 9550; https://doi.org/10.3390/ijms21249550 - 15 Dec 2020
Cited by 24 | Viewed by 4931
Abstract
Cell-free RNAs have the potential to act as a means of gene expression regulation between cells and are therefore used as diagnostic markers describing the state of tissue environment. The origin and functions of such RNAs in human ovarian follicle, the environment of [...] Read more.
Cell-free RNAs have the potential to act as a means of gene expression regulation between cells and are therefore used as diagnostic markers describing the state of tissue environment. The origin and functions of such RNAs in human ovarian follicle, the environment of oocyte maturation, are unclear. The current study investigates the difference in the microRNA profiles of fertile women and polycystic ovary syndrome (PCOS) patients in three compartments from the same preovulatory follicle: mural granulosa cells (MGC), cell-free follicular fluid (FF), and extracellular vesicles (EV) of the FF by small RNA sequencing. In silico analysis was used for the prediction and over-representation of targeted pathways for the detected microRNAs. PCOS follicles were distinguished from normal tissue by the differential expression of 30 microRNAs in MGC and 10 microRNAs in FF (FDR < 0.1) that commonly regulate cytokine signaling pathways. The concentration of EV-s was higher in the FF of PCOS patients (p = 0.04) containing eight differentially expressed microRNAs (p < 0.05). In addition, we present the microRNA profiles of MGC, FF, and EV in the fertile follicle and demonstrate that microRNAs loaded into EVs target mRNAs of distinct signaling pathways in comparison to microRNAs in FF. To conclude, the three follicular compartments play distinct roles in the signaling disturbances associated with PCOS. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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22 pages, 3105 KiB  
Article
Small Non-Coding RNAome of Ageing Chondrocytes
by Panagiotis Balaskas, Jonathan A. Green, Tariq M. Haqqi, Philip Dyer, Yalda A. Kharaz, Yongxiang Fang, Xuan Liu, Tim J.M. Welting and Mandy J. Peffers
Int. J. Mol. Sci. 2020, 21(16), 5675; https://doi.org/10.3390/ijms21165675 - 7 Aug 2020
Cited by 20 | Viewed by 3844
Abstract
Ageing is a leading risk factor predisposing cartilage to osteoarthritis. However, little research has been conducted on the effect of ageing on the expression of small non-coding RNAs (sncRNAs). RNA from young and old chondrocytes from macroscopically normal equine metacarpophalangeal joints was extracted [...] Read more.
Ageing is a leading risk factor predisposing cartilage to osteoarthritis. However, little research has been conducted on the effect of ageing on the expression of small non-coding RNAs (sncRNAs). RNA from young and old chondrocytes from macroscopically normal equine metacarpophalangeal joints was extracted and subjected to small RNA sequencing (RNA-seq). Differential expression analysis was performed in R using package DESeq2. For transfer RNA (tRNA) fragment analysis, tRNA reads were aligned to horse tRNA sequences using Bowtie2 version 2.2.5. Selected microRNA (miRNAs or miRs) and small nucleolar RNA (snoRNA) findings were validated using real-time quantitative Polymerase Chain Reaction (qRT-PCR) in an extended cohort of equine chondrocytes. tRNA fragments were further investigated in low- and high-grade OA human cartilage tissue. In total, 83 sncRNAs were differentially expressed between young and old equine chondrocytes, including miRNAs, snoRNAs, small nuclear RNAs (snRNAs), and tRNAs. qRT-PCR analysis confirmed findings. tRNA fragment analysis revealed that tRNA halves (tiRNAs), tiRNA-5035-GluCTC and tiRNA-5031-GluCTC-1 were reduced in both high grade OA human cartilage and old equine chondrocytes. For the first time, we have measured the effect of ageing on the expression of sncRNAs in equine chondrocytes. Changes were detected in a number of different sncRNA species. This study supports a role for sncRNAs in ageing cartilage and their potential involvement in age-related cartilage diseases. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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15 pages, 3707 KiB  
Article
Gga-miR-3525 Targets PDLIM3 through the MAPK Signaling Pathway to Regulate the Proliferation and Differentiation of Skeletal Muscle Satellite Cells
by Huadong Yin, Jing Zhao, Haorong He, Yuqi Chen, Yan Wang, Diyan Li and Qing Zhu
Int. J. Mol. Sci. 2020, 21(15), 5573; https://doi.org/10.3390/ijms21155573 - 4 Aug 2020
Cited by 22 | Viewed by 3897
Abstract
MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that post-transcriptionally regulate expression of their target genes. Emerging evidence demonstrates that miRNAs are important regulators in the development of skeletal muscle satellite cells (SMSCs). Our previous research showed that gga-miR-3525 is differentially expressed in [...] Read more.
MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that post-transcriptionally regulate expression of their target genes. Emerging evidence demonstrates that miRNAs are important regulators in the development of skeletal muscle satellite cells (SMSCs). Our previous research showed that gga-miR-3525 is differentially expressed in breast muscle of broilers (high growth rate) and layers (low growth rate). In this study, we report a new role for gga-miR-3525 as a myogenic miRNA that regulates skeletal muscle development in chickens. Exogenous increases in the expression of gga-miR-3525 significantly inhibited proliferation and differentiation of SMSCs, whereas the opposite effects were observed in gga-miR-3525 knockdown SMSCs. We confirmed that PDLIM3 (PDZ and LIM domain 3) is a target gene of gga-miR-3525 that can promote proliferation and differentiation of SMSCs. We found that PDLIM3 overexpression elevated the abundance of phosphorylated (p-)p38 protein but that the gga-miR-3525 mimic and p38-MAPK inhibitor (SB203580) weakened the activation of p-p38. Furthermore, treatment with SB203580 reduced the promoting effect of PDLIM3 on SMSC proliferation and differentiation. Overall, our results indicate that gga-miR-3525 regulates the proliferation and differentiation of SMSCs by targeting PDLIM3 via the p38/MAPK signaling pathway in chickens. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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12 pages, 2732 KiB  
Article
The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors
by Ugne Gyvyte, Rokas Lukosevicius, Ruta Inciuraite, Greta Streleckiene, Greta Gudoityte, Justina Bekampyte, Serena Valentini, Violeta Salteniene, Paulius Ruzgys, Saulius Satkauskas, Kristina Zviniene, Juozas Kupcinskas and Jurgita Skieceviciene
Int. J. Mol. Sci. 2020, 21(14), 5151; https://doi.org/10.3390/ijms21145151 - 21 Jul 2020
Cited by 15 | Viewed by 3540
Abstract
Deregulated microRNA (miRNA) expression profiles and their contribution to carcinogenesis have been observed in virtually all types of human cancer. However, their role in the pathogenesis of rare mesenchymal gastrointestinal stromal tumors (GISTs) is not well defined, yet. In this study, we aimed [...] Read more.
Deregulated microRNA (miRNA) expression profiles and their contribution to carcinogenesis have been observed in virtually all types of human cancer. However, their role in the pathogenesis of rare mesenchymal gastrointestinal stromal tumors (GISTs) is not well defined, yet. In this study, we aimed to investigate the role of two miRNAs strongly downregulated in GIST—miR-375-3p and miR-200b-3p—in the pathogenesis of GIST. To achieve this, miRNA mimics were transfected into GIST-T1 cells and changes in the potential target gene mRNA and protein expression, as well as alterations in cell viability, migration, apoptotic cell counts and direct miRNA–target interaction, were evaluated. Results revealed that overexpression of miR-375-3p downregulated the expression of KIT mRNA and protein by direct binding to KIT 3′UTR, reduced GIST cell viability and migration rates. MiR-200b-3p lowered expression of ETV1 protein, directly targeted and lowered expression of EGFR mRNA and protein, and negatively affected cell migration rates. To conclude, the present study identified that miR-375-3p and miR-200b-3p have a tumor-suppressive role in GIST. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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17 pages, 3576 KiB  
Article
Identification and Characterization of Circular Intronic RNAs Derived from Insulin Gene
by Debojyoti Das, Aniruddha Das, Mousumi Sahu, Smruti Sambhav Mishra, Shaheerah Khan, Pruthvi R. Bejugam, Pranita K. Rout, Arundhati Das, Shehnaz Bano, Gyan Prakash Mishra, Sunil K. Raghav, Anshuman Dixit and Amaresh C. Panda
Int. J. Mol. Sci. 2020, 21(12), 4302; https://doi.org/10.3390/ijms21124302 - 17 Jun 2020
Cited by 13 | Viewed by 4522
Abstract
Circular RNAs (circRNAs) are a large family of noncoding RNAs that have emerged as novel regulators of gene expression. However, little is known about the function of circRNAs in pancreatic β-cells. Here, transcriptomic analysis of mice pancreatic islet RNA-sequencing data identified 77 differentially [...] Read more.
Circular RNAs (circRNAs) are a large family of noncoding RNAs that have emerged as novel regulators of gene expression. However, little is known about the function of circRNAs in pancreatic β-cells. Here, transcriptomic analysis of mice pancreatic islet RNA-sequencing data identified 77 differentially expressed circRNAs between mice fed with a normal diet and a high-fat diet. Surprisingly, multiple circRNAs were derived from the intron 2 of the preproinsulin 2 (Ins2) gene and are termed as circular intronic (ci)-Ins2. The expression of ci-Ins2 transcripts in mouse pancreatic islets, and βTC6 cells were confirmed by reverse transcription PCR, DNA sequencing, and RNase R treatment experiments. The level of ci-Ins2 was altered in βTC6 cells upon exposure to elevated levels of palmitate and glucose. Computational analysis predicted the interaction of several RNA-binding proteins with ci-Ins2 and their flanking region, suggesting their role in the ci-Ins2 function or biogenesis. Additionally, bioinformatics analysis predicted the association of several microRNAs with ci-Ins2. Gene ontology and pathway analysis of genes targeted by miRNAs associated with ci-Ins2 suggested the regulation of several key biological processes. Together, our findings indicate that differential expression of circRNAs, especially ci-Ins2 transcripts, may regulate β-cell function and may play a critical role in the development of diabetes. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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Review

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22 pages, 1011 KiB  
Review
Recent Progress on Relevant microRNAs in Autism Spectrum Disorders
by Xingwang Wu, Wanran Li and Yun Zheng
Int. J. Mol. Sci. 2020, 21(16), 5904; https://doi.org/10.3390/ijms21165904 - 17 Aug 2020
Cited by 26 | Viewed by 4790
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathogenesis is unclear and is affected by both genetic and environmental factors. The microRNAs (miRNAs) are a kind of single-stranded non-coding RNA with 20-22 nucleotides, which normally inhibit their target mRNAs at a post-transcriptional [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathogenesis is unclear and is affected by both genetic and environmental factors. The microRNAs (miRNAs) are a kind of single-stranded non-coding RNA with 20-22 nucleotides, which normally inhibit their target mRNAs at a post-transcriptional level. miRNAs are involved in almost all biological processes and are closely related to ASD and many other diseases. In this review, we summarize relevant miRNAs in ASD, and analyze dysregulated miRNAs in brain tissues and body fluids of ASD patients, which may contribute to the pathogenesis and diagnosis of ASD. Full article
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function 2020)
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