Quaking RNA-Binding Proteins Control Early Myofibril Formation by Modulating Tropomyosin
Aline Bonnet1, Guillaume Lambert1, Sylvain Ernest1
1IBENS, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France; INSERM U1024, 75005 Paris, France; CNRS UMR 8197, 75005 Paris, France.
Developmental Cell
|September 5, 2017
Summary
Quaking RNA-binding proteins are crucial for the initial assembly of myofibrils in zebrafish muscle cells. This pathway regulates tropomyosin-3.12 accumulation, impacting myofibril formation and potentially congenital myopathies.
Area of Science:
- Molecular Biology
- Developmental Biology
- Muscle Physiology
Background:
- Skeletal muscle contraction relies on myofibrils, composed of sarcomeres.
- The molecular mechanisms of myofibril assembly during muscle differentiation are not fully understood.
Purpose of the Study:
- To investigate the role of Quaking RNA-binding proteins in myofibril formation.
- To identify the molecular targets and pathways regulated by Quaking in muscle development.
Main Methods:
- Zebrafish model system for genetic interference studies.
- RNA sequencing to identify differentially expressed transcripts.
- Functional analysis of gene targets in myofibril assembly.
Main Results:
- Quaking proteins are essential for early myofibril assembly in zebrafish.
- Quaking regulates the accumulation of the tropomyosin-3.12 (tpm3.12) transcript.
- A specific Quaking-binding site in the tpm3.12 3' UTR is critical for its accumulation and myofibril formation.
Conclusions:
- A novel Quaking/Tpm3.12 pathway controls de novo myofibril assembly.
- Dysregulation of this pathway may contribute to congenital myopathies associated with TPM3 mutations.
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