Abstract
BackgroundLa-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.MethodsTo uncover the role of LARP6 in development, we utilized Morpholino Oligos to deplete LARP6 protein in Xenopus embryos. 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).ResultsWe knocked down LARP6 in Xenopus embryos 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 of mcidas in a Notch-independent manner.ConclusionsLa-related protein 6 is involved in ciliated cell differentiation during development by controlling the expression of cilia-related genes including mcidas. This LARP6 function involves a mechanism that is distinct from its established role in binding to collagen mRNAs and regulating their translation.
Highlights
La-related protein 6 (LARP6) is an evolutionally conserved RNA-binding protein
Since type I collagen expression begins at the late neurula stage in Xenopus embryos [33], the expression pattern suggests that LARP6 may have additional functions during Xenopus development
The effect of LARP6 MO (L6MO) is highly specific to Xenopus LARP6, because it could not block the synthesis of the homologous human LARP6 protein (HA-hL6) expressed in Xenopus embryos (Fig. 1d)
Summary
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. The cilium is a motile or non-motile cellular protrusion that is essential for cell physiology, development and organ homeostasis [1,2,3]. Non-motile primary cilia sense physical and biochemical extracellular signals in a variety of Recent progress in RNA biology has shown that RNAbinding proteins (RBPs) are important post-transcriptional regulators [5]. BicC mediates the alignment of cilia at the left–right organizer, possibly by regulating the activity of the canonical Wnt pathway through Dvl and/or RNA silencing in P-bodies [6]. The post-transcriptional regulation by RBPs is likely an important level of regulatory control for ciliogenesis, the RBPs involved and their regulatory mechanisms remain largely undiscovered
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