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Dev Cell. 2017 Sep 11;42(5):527-541.e4. doi: 10.1016/j.devcel.2017.08.004. Epub 2017 Aug 31.

Quaking RNA-Binding Proteins Control Early Myofibril Formation by Modulating Tropomyosin.

Author information

1
IBENS, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France; INSERM U1024, 75005 Paris, France; CNRS UMR 8197, 75005 Paris, France. Electronic address: bonnet.aline@gmail.com.
2
IBENS, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France; INSERM U1024, 75005 Paris, France; CNRS UMR 8197, 75005 Paris, France.
3
INSERM U1024, 75005 Paris, France; CNRS UMR 8197, 75005 Paris, France; IBENS, Institut de Biologie de l'Ecole Normale Supérieure, Plateforme Génomique, 75005 Paris, France.
4
IBENS, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France; INSERM U1024, 75005 Paris, France; CNRS UMR 8197, 75005 Paris, France. Electronic address: rosa@biologie.ens.fr.

Abstract

Skeletal muscle contraction is mediated by myofibrils, complex multi-molecular scaffolds structured into repeated units, the sarcomeres. Myofibril structure and function have been extensively studied, but the molecular processes regulating its formation within the differentiating muscle cell remain largely unknown. Here we show in zebrafish that genetic interference with the Quaking RNA-binding proteins disrupts the initial steps of myofibril assembly without affecting early muscle differentiation. Using RNA sequencing, we demonstrate that Quaking is required for accumulation of the muscle-specific tropomyosin-3 transcript, tpm3.12. Further functional analyses reveal that Tpm3.12 mediates Quaking control of myofibril formation. Moreover, we identified a Quaking-binding site in the 3' UTR of tpm3.12 transcript, which is required in vivo for tpm3.12 accumulation and myofibril formation. Our work uncovers a Quaking/Tpm3 pathway controlling de novo myofibril assembly. This unexpected developmental role for Tpm3 could be at the origin of muscle defects observed in human congenital myopathies associated with tpm3 mutation.

KEYWORDS:

Quaking; RNA-binding protein; embryo; muscle; myofibril; tropomyosin; zebrafish

PMID:
28867488
DOI:
10.1016/j.devcel.2017.08.004
[Indexed for MEDLINE]
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