Conserved functions of RNA-binding proteins in muscle

Nikonova, Elena; Kao, Shao-Yen; Ravichandran, Keshika; Wittner, Anja; Spletter, Maria L.

doi:10.1016/j.biocel.2019.02.008

Cited by 23 publications

(60 citation statements)

References 407 publications

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“…Bioinformatics analysis can be used to identify IFM enriched genes or proteins, but further experiments are required to demonstrate that they are in fact IFM-specific. Sample purity can be assayed using published tissue-specific markers such as Stripe 45 (tendon), Act79B 4,44 (tubular muscle), Act88F 15 (IFM), or syb 46 (neuronal specific).…”

Section: Discussionmentioning

confidence: 99%

“…In a second example, studies from cell culture, animal models, and human patients have shown that myotonic dystrophy is caused by a disruption in RNA regulation due to sequestration of Muscleblind (MBNL) and upregulation of CELF1 4,5 . The cross-regulatory and temporal dynamics between MBNL and CELF1 (also called CUGBP1 or Bruno-Like 2) help to explain the persistent embryonic splicing patterns in myotonic dystrophy patients.…”

Section: Introductionmentioning

confidence: 99%

“…The cross-regulatory and temporal dynamics between MBNL and CELF1 (also called CUGBP1 or Bruno-Like 2) help to explain the persistent embryonic splicing patterns in myotonic dystrophy patients. Additionally, the large network of misregulated targets helps to explain the complex nature of the disease 4,6,7,8 . A majority of such studies utilize omics approaches in genetic model organisms to understand the mechanisms underlying human muscle disease.…”

Section: Introductionmentioning

confidence: 99%

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Dissection of <em>Drosophila melanogaster</em> Flight Muscles for Omics Approaches

Kao¹,

Nikonova²,

Ravichandran³

et al. 2019

JoVE

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Drosophila flight muscle is a powerful model to study diverse processes such as transcriptional regulation, alternative splicing, metabolism, and mechanobiology, which all influence muscle development and myofibrillogenesis. Omics data, such as those generated by mass spectrometry or deep sequencing, can provide important mechanistic insights into these biological processes. For such approaches, it is beneficial to analyze tissue-specific samples to increase both selectivity and specificity of the omics fingerprints. Here we present a protocol for dissection of fluorescent-labeled flight muscle from live pupae to generate highly enriched muscle samples for omics applications. We first describe how to dissect flight muscles at early pupal stages (<48 h after puparium formation [APF]), when the muscles are discernable by green fluorescent protein (GFP) labeling. We then describe how to dissect muscles from late pupae (>48 h APF) or adults, when muscles are distinguishable under a dissecting microscope. The accompanying video protocol will make these technically demanding dissections more widely accessible to the muscle and Drosophila research communities. For RNA applications, we assay the quantity and quality of RNA that can be isolated at different time points and with different approaches. We further show that Bruno1 (Bru1) is necessary for a temporal shift in myosin heavy chain (Mhc) splicing, demonstrating that dissected muscles can be used for mRNA-Seq, mass spectrometry, and reverse transcription polymerase chain reaction (RT-PCR) applications. This dissection protocol will help promote tissue-specific omics analyses and can be generally applied to study multiple biological aspects of myogenesis. Video Link The video component of this article can be found at https://www.jove.com/video/60309/ Drosophila melanogaster is another well-established genetic model organism. The structure of the sarcomere as well as individual sarcomere components are highly conserved from flies to vertebrates 4,9,10 , and the indirect flight muscles (IFMs) have become a powerful model to study multiple aspects of muscle development 11,12. First, the fibrillar flight muscles are functionally and morphologically distinct from tubular body muscles 11,13 , allowing investigation of muscle-type specific developmental mechanisms. Transcription factors including Spalt major (Salm) 14 , Extradenticle (Exd), and Homothorax (Hth) 15 have been identified as fibrillar fate regulators. Additionally, downstream of Salm, the CELF1 homolog Bruno1 (Bru1, Aret) directs a fibrillar-specific splicing program 16,17. Second, IFMs are an important model for understanding the process of myogenesis itself, from myoblast fusion and myotube attachment to myofibrillogenesis and sarcomere maturation 9,18,19. Third, Drosophila genetics permits investigation of contributions by individual proteins, protein domains, and protein isoforms to sarcomere formation, function, and biophysical properties 20,21,22,23. Lastly, IFM models have been developed for the study of...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dissection of <em>Drosophila melanogaster</em> Flight Muscles for Omics Approaches

Kao¹,

Nikonova²,

Ravichandran³

et al. 2019

JoVE

Self Cite

View full text Add to dashboard Cite

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“…Thus, Rbm24 may represent an important conserved regulator of muscle-specific alternative splicing events in skeletal muscles. At present, the transcriptional control of muscle cell specification and differentiation has been relatively well documented [ 52 , 53 ], but the contribution of post-transcriptional regulation to muscle development remains largely unclear [ 54 ]. However, misregulation of several RBPs, including CELF (CUG-BP, Elav-like family), MBNL (Muscleblind-like) and RBFOX (RNA-binding forkhead box) families of proteins, disrupts muscle-specific alternative splicing and has been linked to skeletal muscle disease such as myotonic dystrophy [ 7 , 54 ].…”

Section: Rbm24 Regulates Muscle Cell Development Through Distinct mentioning

confidence: 99%

“…At present, the transcriptional control of muscle cell specification and differentiation has been relatively well documented [ 52 , 53 ], but the contribution of post-transcriptional regulation to muscle development remains largely unclear [ 54 ]. However, misregulation of several RBPs, including CELF (CUG-BP, Elav-like family), MBNL (Muscleblind-like) and RBFOX (RNA-binding forkhead box) families of proteins, disrupts muscle-specific alternative splicing and has been linked to skeletal muscle disease such as myotonic dystrophy [ 7 , 54 ]. Since skeletal muscle is one of the first tissues in which alternative splicing generates abundant contractile proteins from widely expressed genes has been identified [ 55 ], these observations provide mechanistic insights into muscle cell differentiation and function.…”

Section: Rbm24 Regulates Muscle Cell Development Through Distinct mentioning

confidence: 99%

RNA-Binding Protein Rbm24 as a Multifaceted Post-Transcriptional Regulator of Embryonic Lineage Differentiation and Cellular Homeostasis

Grifone

Shao

Saquet

et al. 2020

Cells

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RNA-binding proteins control the metabolism of RNAs at all stages of their lifetime. They are critically required for the post-transcriptional regulation of gene expression in a wide variety of physiological and pathological processes. Rbm24 is a highly conserved RNA-binding protein that displays strongly regionalized expression patterns and exhibits dynamic changes in subcellular localization during early development. There is increasing evidence that it acts as a multifunctional regulator to switch cell fate determination and to maintain tissue homeostasis. Dysfunction of Rbm24 disrupts cell differentiation in nearly every tissue where it is expressed, such as skeletal and cardiac muscles, and different head sensory organs, but the molecular events that are affected may vary in a tissue-specific, or even a stage-specific manner. Recent works using different animal models have uncovered multiple post-transcriptional regulatory mechanisms by which Rbm24 functions in key developmental processes. In particular, it represents a major splicing factor in muscle cell development, and plays an essential role in cytoplasmic polyadenylation during lens fiber cell terminal differentiation. Here we review the advances in understanding the implication of Rbm24 during development and disease, by focusing on its regulatory roles in physiological and pathological conditions.

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To RNA‐binding and beyond: Emerging facets of the role of Rbfox proteins in development and disease

Mukherjee,

Nongthomba

2023

WIREs RNA

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The RNA‐binding Fox‐1 homologue (Rbfox) proteins represent an ancient family of splicing factors, conserved through evolution. All members share an RNA recognition motif (RRM), and a particular affinity for the GCAUG signature in target RNA molecules. The role of Rbfox, as a splice factor, deciding the tissue‐specific inclusion/exclusion of an exon, depending on its binding position on the flanking introns, is well known. Rbfox often acts in concert with other splicing factors, and forms splicing regulatory networks. Apart from this canonical role, recent studies show that Rbfox can also function as a transcription co‐factor, and affects mRNA stability and translation. The repertoire of Rbfox targets is vast, including genes involved in the development of tissue lineages, such as neurogenesis, myogenesis, and erythropoeiesis, and molecular processes, including cytoskeletal dynamics, and calcium handling. A second layer of complexity is added by the fact that Rbfox expression itself is regulated by multiple mechanisms, and, in vertebrates, exhibits tissue‐specific expression. The optimum dosage of Rbfox is critical, and its misexpression is etiological to various disease conditions. In this review, we discuss the contextual roles played by Rbfox as a tissue‐specific regulator for the expression of many important genes with diverse functions, through the lens of the emerging data which highlights its involvement in many human diseases. Furthermore, we explore the mechanistic details provided by studies in model organisms, with emphasis on the work with Drosophila.This article is categorized under: RNA Processing > Splicing Mechanisms RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications RNA Turnover and Surveillance > Regulation of RNA Stability RNA Processing > Splicing Regulation/Alternative Splicing

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Conserved functions of RNA-binding proteins in muscle

Cited by 23 publications

References 407 publications

Dissection of <em>Drosophila melanogaster</em> Flight Muscles for Omics Approaches

Dissection of <em>Drosophila melanogaster</em> Flight Muscles for Omics Approaches

RNA-Binding Protein Rbm24 as a Multifaceted Post-Transcriptional Regulator of Embryonic Lineage Differentiation and Cellular Homeostasis

To RNA‐binding and beyond: Emerging facets of the role of Rbfox proteins in development and disease

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