Developmental Cell
Volume 42, Issue 5, 11 September 2017, Pages 527-541.e4
Journal home page for Developmental Cell

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

https://doi.org/10.1016/j.devcel.2017.08.004Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Quaking (Qki) RNA-binding proteins control de novo muscle myofibril formation

  • Qki is required for the accumulation of the muscle-specific tropomyosin-3 transcript

  • This regulation requires a Qki-binding site in the tropomyosin-3 3′ UTR

  • Tropomyosin-3 mediates Qki control of early myofibril formation

Summary

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

muscle
myofibril
zebrafish
embryo
Quaking
RNA-binding protein
tropomyosin

Cited by (0)

5

Present address: Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS URA 2578, 75015 Paris, France

6

Present address: SABNP, Inserm U1204, University of Evry, 91000 Evry, France

7

Present address: Blueprint Medicines, 38 Sidney Street, Cambrige, MA 02139, USA

8

Lead Contact