Computational Design of Artificial RNA Molecules for Gene Regulation

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

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Regulatory RNA molecules

Microbiology Australia ◽

10.1071/ma06124 ◽

2006 ◽

Vol 27 (3) ◽

pp. 124

Author(s):

Stephen M Kwong ◽

Neville Firth

Keyword(s):

Gene Regulation ◽

Antisense Rna ◽

Current Knowledge ◽

Regulatory Rna ◽

Rna Molecules ◽

Genetic Elements ◽

Regulatory Systems ◽

Regulatory Rnas

Numerous examples of antisense RNA-mediated gene regulation have been found in bacteria. Such regulatory systems were first identified on accessory genetic elements such as plasmids, transposons and phages, and it is from these that most of our current knowledge of regulatory RNAs is drawn.

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Nutritive implications of dietary microRNAs: facts, controversies, and perspectives

Food & Function ◽

10.1039/c9fo00216b ◽

2019 ◽

Vol 10 (6) ◽

pp. 3044-3056 ◽

Cited By ~ 1

Author(s):

Jianting Li ◽

Lin Lei ◽

Fayin Ye ◽

Yun Zhou ◽

Hui Chang ◽

...

Keyword(s):

Gene Regulation ◽

Pivotal Role ◽

Rna Molecules ◽

Non Coding Rna

As a group of non-coding RNA molecules, microRNAs have recently become more well-known due to their pivotal role in gene regulation.

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Computational Design of a Circular RNA with Prionlike Behavior

Artificial Life ◽

10.1162/artl_a_00197 ◽

2016 ◽

Vol 22 (2) ◽

pp. 172-184 ◽

Cited By ~ 1

Author(s):

Stefan Badelt ◽

Christoph Flamm ◽

Ivo L. Hofacker

Keyword(s):

Synthetic Biology ◽

Structure Formation ◽

Computational Methods ◽

Computational Design ◽

Circular Rna ◽

Equilibrium Thermodynamics ◽

Rna Molecules ◽

Rna Design ◽

Kinetics Of ◽

Functional Rna

RNA molecules engineered to fold into predefined conformations have enabled the design of a multitude of functional RNA devices in the field of synthetic biology and nanotechnology. More complex designs require efficient computational methods, which need to consider not only equilibrium thermodynamics but also the kinetics of structure formation. Here we present a novel type of RNA design that mimics the behavior of prions, that is, sequences capable of interaction-triggered autocatalytic replication of conformations. Our design was computed with the ViennaRNA package and is based on circular RNA that embeds domains amenable to intermolecular kissing interactions.

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MicroRNAs in skin and wound healing

Physiological Genomics ◽

10.1152/physiolgenomics.00157.2010 ◽

2011 ◽

Vol 43 (10) ◽

pp. 543-556 ◽

Cited By ~ 78

Author(s):

Jaideep Banerjee ◽

Yuk Cheung Chan ◽

Chandan K. Sen

Keyword(s):

Wound Healing ◽

Gene Regulation ◽

Skin Diseases ◽

Mrna Degradation ◽

Messenger Rnas ◽

Skin Development ◽

Rna Molecules ◽

Posttranscriptional Gene Regulation

MicroRNAs (miRNAs) are small endogenous RNA molecules ∼22 nt in length. miRNAs are capable of posttranscriptional gene regulation by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of translation. miRNAs have recently been shown to play pivotal roles in skin development and are linked to various skin pathologies, cancer, and wound healing. This review focuses on the role of miRNAs in cutaneous biology, the various methods of miRNA modulation, and the therapeutic opportunities in treatment of skin diseases and wound healing.

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Computational Design of Asymmetric Three-dimensional RNA Structures and Machines

10.1101/223479 ◽

2017 ◽

Cited By ~ 6

Author(s):

Joseph D. Yesselman ◽

Daniel Eiler ◽

Erik D. Carlson ◽

Alexandra N. Ooms ◽

Wipapat Kladwang ◽

...

Keyword(s):

Three Dimensional ◽

Computational Design ◽

Chemical Mapping ◽

Rna Structures ◽

Single Nucleotide ◽

Rna Molecules ◽

Rna Nanotechnology ◽

X Ray Scattering ◽

Nucleotide Resolution ◽

Large Sections

AbstractThe emerging field of RNA nanotechnology seeks to create nanoscale 3D machines by repurposing natural RNA modules, but successes have been limited to symmetric assemblies of single repeating motifs. We present RNAMake, a suite that automates design of RNA molecules with complex 3D folds. We first challenged RNAMake with the paradigmatic problem of aligning a tetraloop and sequence-distal receptor, previously only solved via symmetry. Single-nucleotide-resolution chemical mapping, native gel electrophoresis, and solution x-ray scattering confirmed that 11 of the 16 ‘miniTTR’ designs successfully achieved clothespin-like folds. A 2.55 Å diffraction-resolution crystal structure of one design verified formation of the target asymmetric nanostructure, with large sections achieving near-atomic accuracy (< 2.0 Å). Finally, RNAMake designed asymmetric segments to tether the 16S and 23S rRNAs together into a synthetic singlestranded ribosome that remains uncleaved by ribonucleases and supports life in Escherichia coli, a challenge previously requiring several rounds of trial-and-error.

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RNA Interference in Fungi: Pathways, Functions, and Applications

Eukaryotic Cell ◽

10.1128/ec.05109-11 ◽

2011 ◽

Vol 10 (9) ◽

pp. 1148-1155 ◽

Cited By ~ 111

Author(s):

Yunkun Dang ◽

Qiuying Yang ◽

Zhihong Xue ◽

Yi Liu

Keyword(s):

Gene Regulation ◽

Rna Interference ◽

Small Rna ◽

Rnai Machinery ◽

Content Type ◽

Heterochromatin Formation ◽

Rna Molecules ◽

Cellular Processes ◽

Rna Biogenesis ◽

Core Components

ABSTRACT Small RNA molecules of about 20 to 30 nucleotides function in gene regulation and genomic defense via conserved eukaryotic RNA interference (RNAi)-related pathways. The RNAi machinery consists of three core components: Dicer, Argonaute, and RNA-dependent RNA polymerase. In fungi, the RNAi-related pathways have three major functions: genomic defense, heterochromatin formation, and gene regulation. Studies of Schizosaccharomyces pombe and Neurospora , and other fungi have uncovered surprisingly diverse small RNA biogenesis pathways, suggesting that fungi utilize RNAi-related pathways in various cellular processes to adapt to different environmental conditions. These studies also provided important insights into how RNAi functions in eukaryotic systems in general. In this review, we will discuss our current understanding of the fungal RNAi-related pathways and their functions, with a focus on filamentous fungi. We will also discuss how RNAi can be used as a tool in fungal research.

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Effectiveness and Usability of Bioinformatics Tools to Analyze Pathways Associated with miRNA Expression

Cancer Informatics ◽

10.4137/cin.s32716 ◽

2015 ◽

Vol 14 ◽

pp. CIN.S32716 ◽

Cited By ~ 3

Author(s):

Lila E. Mullany ◽

Roger K. Wolff ◽

Martha L. Slattery

Keyword(s):

Gene Ontology ◽

Gene Regulation ◽

Mirna Expression ◽

Biological Pathways ◽

Colorectal Tumors ◽

Rna Molecules ◽

General Lack ◽

Bioinformatic Tools ◽

Bioinformatics Tools ◽

Differentially Expressed Mirnas

MiRNAs are small, nonprotein-coding RNA molecules involved in gene regulation. While bioinformatics help guide miRNA research, it is less clear how they perform when studying biological pathways. We used 13 criteria to evaluate effectiveness and usability of existing bioinformatics tools. We evaluated the performance of six bioinformatics tools with a cluster of 12 differentially expressed miRNAs in colorectal tumors and three additional sets of 12 miRNAs that are not part of a known cluster. MiRPath performed the best of all the tools in linking miRNAs, with 92% of all miRNAs linked as well as the highest based on our established criteria followed by Ingenuity (58% linked). Other tools, including Empirical Gene Ontology, miRó, miRMaid, and PhenomiR, were limited by their lack of available tutorials, lack of flexibility and interpretability, and/or difficulty using the tool. In summary, we observed a lack of standardization across bioinformatic tools and a general lack of specificity in terms of pathways identified between groups of miRNAs. Hopefully, this evaluation will help guide the development of new tools.

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Computational design of small transcription activating RNAs for versatile and dynamic gene regulation

Nature Communications ◽

10.1038/s41467-017-01082-6 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 49

Author(s):

James Chappell ◽

Alexandra Westbrook ◽

Matthew Verosloff ◽

Julius B. Lucks

Keyword(s):

Gene Regulation ◽

Computational Design

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Mitochondrial Gene Expression and Beyond—Novel Aspects of Cellular Physiology

Cells ◽

10.3390/cells9010017 ◽

2019 ◽

Vol 9 (1) ◽

pp. 17 ◽

Cited By ~ 5

Author(s):

Anna V. Kotrys ◽

Roman J. Szczesny

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Mitochondrial Gene ◽

Proper Function ◽

Cell Physiology ◽

Mitochondrial Gene Expression ◽

Rna Molecules ◽

Health And Disease ◽

Mitochondrial Transcripts ◽

Human Mitochondrial Genome

Mitochondria are peculiar organelles whose proper function depends on the crosstalk between two genomes, mitochondrial and nuclear. The human mitochondrial genome (mtDNA) encodes only 13 proteins; nevertheless, its proper expression is essential for cellular homeostasis, as mtDNA-encoded proteins are constituents of mitochondrial respiratory complexes. In addition, mtDNA expression results in the production of RNA molecules, which influence cell physiology once released from the mitochondria into the cytoplasm. As a result, dysfunctions of mtDNA expression may lead to pathologies in humans. Here, we review the mechanisms of mitochondrial gene expression with a focus on recent findings in the field. We summarize the complex turnover of mitochondrial transcripts and present an increasing body of evidence indicating new functions of mitochondrial transcripts. We discuss mitochondrial gene regulation in different cellular contexts, focusing on stress conditions. Finally, we highlight the importance of emerging aspects of mitochondrial gene regulation in human health and disease.

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