La-related protein 6 controls ciliated cell differentiation.
BACKGROUND
La-related protein 6 (LARP6) is an evolutionally conserved RNA-binding protein. Vertebrate LARP6 binds the 5' stem-loop found in mRNAs encoding type I collagen to regulate their translation, but other target mRNAs and additional functions for LARP6 are unknown. The aim of this study was to elucidate an additional function of LARP6 and to evaluate the importance of its function during development.


METHODS
To uncover the role of LARP6 in development, we utilized Morpholino Oligos to deplete LARP6 protein inXenopusembryos. Then, embryonic phenotypes and ciliary structures of LAPR6 morphants were examined. To identify the molecular mechanism underlying ciliogenesis regulated by LARP6, we tested the expression level of cilia-related genes, which play important roles in ciliogenesis, by RT-PCR or whole mount in situ hybridization (WISH).


RESULTS
We knocked down LARP6 inXenopusembryos and found neural tube closure defects. LARP6 mutant, which compromises the collagen synthesis, could rescue these defects. Neural tube closure defects are coincident with lack of cilia, antenna-like cellular organelles with motility- or sensory-related functions, in the neural tube. The absence of cilia at the epidermis was also observed in LARP6 morphants, and this defect was due to the absence of basal bodies which are formed from centrioles and required for ciliary assembly. In the process of multi-ciliated cell (MCC) differentiation, mcidas, which activates the transcription of genes required for centriole formation during ciliogenesis, could partially restore MCCs in LARP6 morphants. In addition, LARP6 likely controls the expression ofmcidasin a Notch-independent manner.


CONCLUSIONS
La-related protein 6 is involved in ciliated cell differentiation during development by controlling the expression of cilia-related genes includingmcidas. This LARP6 function involves a mechanism that is distinct from its established role in binding to collagen mRNAs and regulating their translation.
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.|Department of Translational Genomics, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089-9601 USA.
Zarko
Z
Manojlovic
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Ryan
R
Earwood
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Akiko
A
Kato
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Diana
D
Perez
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Oscar A
OA
Cabrera
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Ruth
R
Didier
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Timothy L
TL
Megraw
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Branko
B
Stefanovic
Department of Biomedical Sciences, Florida State University College of Medicine, 1115W. Call Street, Tallahassee, FL 32306-4300 USA.
Yoichi
Y
Kato
Cilia; LARP6; Xenopus; mcidas