Non-coding RNAs in muscle differentiation and musculoskeletal disease

Ballarino, Monica; Morlando, Mariangela; Fatica, Alessandro; Bozzoni, Irene

doi:10.1172/jci84419

Cited by 78 publications

(55 citation statements)

References 128 publications

(141 reference statements)

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“…Through their primary sequence and secondary structure, lncRNAs can bind to other nucleic acids and/or proteins to regulate gene expression programs, in turn controlling a growing number of cellular processes, such as cell division, the stress response, differentiation, survival, and senescence (Audas & Lee, ; Chen, Satpathy, & Chang, ; Grammatikakis, Panda, Abdelmohsen, & Gorospe, ; Li, Tian, Yang, & Gong, ). By affecting these processes, there is increasing appreciation that lncRNAs have a direct impact on the physiology of tissues and organs, and on a growing number of disease processes (e.g., muscle disease, cancer, and cardiovascular pathologies) (Alvarez‐Dominguez & Lodish, ; Ballarino, Morlando, Fatica, & Bozzoni, ; Greco, Gorospe, & Martelli, ; Schmitt & Chang, ; Wang, Xiao, & Wang, ). Despite intense efforts, however, only a small number of lncRNAs have been characterized functionally, while the vast majority of lncRNAs have no known functions at present.…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic functions of long noncoding RNAs

et al. 2018

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Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides found throughout the cell that lack protein-coding function. Their functions are closely linked to their interaction with RNA-binding proteins (RBPs) and nucleic acids. Nuclear lncRNAs have been studied extensively, revealing complexes with structural and regulatory roles that enable gene organization and control transcription. Cytoplasmic lncRNAs are less well understood, but accumulating evidence indicates that they also form complexes with diverse structural and regulatory functions. Here, we review our current knowledge of cytoplasmic lncRNAs and the different levels of gene regulation controlled by cytoplasmic lncRNA complexes, including mRNA turnover, translation, protein stability, sponging of cytosolic factors, and modulation of signaling pathways. We conclude by discussing areas of future study needed to elucidate comprehensively the biology of lncRNAs, to further understand the impact of lncRNAs on physiology and design lncRNA-centered therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

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Section: Introductionmentioning

confidence: 99%

Cytoplasmic functions of long noncoding RNAs

et al. 2018

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“…lncRNAs, through their ability to interact with nucleic acids as well as with proteins (Guttman & Rinn, ; Rinn & Chang, ; Batista & Chang, ; Cipriano & Ballarino, ), act as scaffolds for the formation of specific functional complexes where different proteins and RNA and even DNA molecules can be tethered together (Wutz et al , ; Clemson et al , ; Tsai et al , ; Ariel et al , ; Hacisuleyman et al , ; Ribeiro et al , ). Nuclear lncRNAs have been described to control the transcriptional myogenic program through diverse modes of action (Ballarino et al , ): as enhancer‐associated transcripts (Mousavi et al , ; Mueller et al , ; Ounzain et al , ), as guides for the recruitment of PRCs and MLL epigenetic regulators or DNA methyltransferases (DNMT; Wang et al , , ), and also as allosteric inhibitors (Han et al , ; Wang et al , ). Important functions have also been ascribed to cytoplasmic lncRNAs through their ability to control mRNA stability and translation (Wang et al , ), to modulate miRNA function acting as competing endogenous RNA (Cesana et al , ; Salmena et al , ; Han et al , ), or to encode for micropeptides (Anderson et al , ; Nelson et al , ).…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice

et al. 2018

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Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and miRNAs, long noncoding RNAs (lncRNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin‐associated muscle‐specific lncRNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo. In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein. Notably, several Charme‐sensitive genes are associated with human cardiomyopathies and Charme depletion in mice results in a peculiar cardiac remodeling phenotype with changes in size, structure, and shape of the heart. Moreover, the existence of an orthologous transcript in human, regulating the same subset of target genes, suggests an important and evolutionarily conserved function for Charme. Altogether, these data describe a new example of a chromatin‐associated lncRNA regulating the robustness of skeletal and cardiac myogenesis.

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“…Numerous tools have been developed to analyze scRNA-seq data, due to its intrinsic features. There are at least 493 tools available on the web [143], covering over 30 categories including quality control, read alignment, normalization, and gene networks analysis. Concluding, scRNA-seq can be performed on full-length RNA or just on its 5 or 3 ends with the consequent necessity of performing the sequencing at a different depth.…”

Section: Rna Sequencing and Bioinformatic Analysismentioning

confidence: 99%

“…In this context, Rizvi and colleagues proposed an algorithm to study transcriptional regulation to identify cell identity over time and therefore cell differentiation in response to specific stimuli. The proposed algorithm, called single-cell topological data analysis (scTDA), does not work as previously developed algorithms that suppose a one or three-like branched structure, but it is based on an unsupervised method that has the advantage of extracting more complex relationships [143]. An interesting feature of this algorithm is that it was able to identify cell states by using lncRNAs supporting the notion of their cell stage-specific expression.…”

Section: Lncrnas In Embryo-derived Cellsmentioning

confidence: 99%

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

Alessio

Bonadio

Buson

et al. 2020

IJMS

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In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated transcripts are long non-coding RNAs (lncRNAs). In contrast to protein-coding RNAs, they show a more cell-specific expression. To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization. Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions. In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification. The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis. We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data. Tables are included to schematize, describe, and compare exposed concepts.Int. J. Mol. Sci. 2020, 21, 302 2 of 32 not achieved by transcription factors (TFs) alone because of their low number (approximately 1500 in mammals [4]) compared to genes to regulate (90% of the genome is transcribed in human [5]). A single TF is estimated to regulate only ten thousand genes according to Chromatin immunoprecipitation and DNA sequencing experiments (ChIp-seq) [6]. Moreover, the involvement of non-coding RNAs in gene expression regulation was evident [7,8]. The evidence that the non-protein coding component of the human genome is actively transcribed and carries out crucial functions limits the importance of coding genes in genome regulation. Non-coding transcripts become one of the stars of modern biology, especially because of their involvement in a wide range of regulatory processes and changed the association of non-coding regions to junk DNA [3].The genome of multicellular eukaryotes is mostly comprised of non-coding DNA (less than 2% of the human genome codes for proteins [9] while 90% of the human genome is transcribed). Non-coding DNA is transcribed into different classes of non-coding RNAs (ncRNAs) that include structural RNAs (rRNAs and tRNAs) and regulatory RNAs [10]. rRNAs and tRNAs are involved in mRNA translation and can be long or short in size. Regulatory RNAs are further divided into three classes: Small, medium, and long non-coding RNAs. Small non-coding RNAs are between 20 and 50 nucleotides long and include microRNAs (miRNAs) that participate in post-transcriptional regulation [11], small interfering RNAs (siRNAs) that are double-stranded RNAs involved in gene silencing through RNA interfering pathway [12], piwi interacting R...

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Non-coding RNAs in muscle differentiation and musculoskeletal disease

Cited by 78 publications

References 128 publications

Cytoplasmic functions of long noncoding RNAs

Cytoplasmic functions of long noncoding RNAs

Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

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