Next Article in Journal
DNA Fingerprint Analysis of Raman Spectra Captures Global Genomic Alterations in Imatinib-Resistant Chronic Myeloid Leukemia: A Potential Single Assay for Screening Imatinib Resistance
Next Article in Special Issue
Chemical Genetic Screen in Drosophila Germline Uncovers Small Molecule Drugs That Sensitize Stem Cells to Insult-Induced Apoptosis
Previous Article in Journal
Role of the Transcriptional Repressor Zinc Finger with KRAB and SCAN Domains 3 (ZKSCAN3) in Retinal Pigment Epithelial Cells
Previous Article in Special Issue
Drosophila Accessory Gland: A Complementary In Vivo Model to Bring New Insight to Prostate Cancer
Article

A Candidate RNAi Screen Reveals Diverse RNA-Binding Protein Phenotypes in Drosophila Flight Muscle

1
Biomedical Center, Department of Physiological Chemistry, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152 Martinsried-Planegg, Germany
2
Department of Biology, University of Wisconsin at Madison, 1117 W. Johnson St., Madison, WI 53706, USA
3
Molecular Nutrition Medicine, Else Kröner-Fresenius Center, Technical University of Munich, 85354 Freising, Germany
4
Biomedical Center, Bioinformatics Core Facility, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152 Martinsried-Planegg, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Krzysztof Jagla
Cells 2021, 10(10), 2505; https://doi.org/10.3390/cells10102505
Received: 4 August 2021 / Revised: 14 September 2021 / Accepted: 18 September 2021 / Published: 22 September 2021
(This article belongs to the Special Issue Drosophila: A Model for Genetic Research)
The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability among muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing, including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently, only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here, we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a powerful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered. View Full-Text
Keywords: RNA binding proteins; SF1; Hrb87F; Bru1; Drosophila; flight muscle; RNAi; splicing RNA binding proteins; SF1; Hrb87F; Bru1; Drosophila; flight muscle; RNAi; splicing
Show Figures

Graphical abstract

MDPI and ACS Style

Kao, S.-Y.; Nikonova, E.; Chaabane, S.; Sabani, A.; Martitz, A.; Wittner, A.; Heemken, J.; Straub, T.; Spletter, M.L. A Candidate RNAi Screen Reveals Diverse RNA-Binding Protein Phenotypes in Drosophila Flight Muscle. Cells 2021, 10, 2505. https://doi.org/10.3390/cells10102505

AMA Style

Kao S-Y, Nikonova E, Chaabane S, Sabani A, Martitz A, Wittner A, Heemken J, Straub T, Spletter ML. A Candidate RNAi Screen Reveals Diverse RNA-Binding Protein Phenotypes in Drosophila Flight Muscle. Cells. 2021; 10(10):2505. https://doi.org/10.3390/cells10102505

Chicago/Turabian Style

Kao, Shao-Yen, Elena Nikonova, Sabrina Chaabane, Albiona Sabani, Alexandra Martitz, Anja Wittner, Jakob Heemken, Tobias Straub, and Maria L. Spletter 2021. "A Candidate RNAi Screen Reveals Diverse RNA-Binding Protein Phenotypes in Drosophila Flight Muscle" Cells 10, no. 10: 2505. https://doi.org/10.3390/cells10102505

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop