La-related protein 6 controls ciliated cell differentiation.
La-related protein 6 controls ciliated cell differentiation.
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作者：
Manojlovic Z;Earwood R;Kato A;Perez D;Cabrera OA;Didier R;Megraw TL;Stefanovic B;Kato Y
La相关蛋白6（LARP 6）是一种进化上保守的RNA结合蛋白。脊椎动物LARP 6结合在编码I型胶原的mRNA中发现的5′茎环来调节其翻译，但LARP 6的其他靶mRNA和其他功能尚不清楚。本研究的目的是阐明LARP 6的额外功能，并评估其功能在发育过程中的重要性。为了揭示LARP 6在发育中的作用，我们利用Morpholino Oligos去除爪蟾胚胎中的LARP 6蛋白。然后，对LAPR 6变体的胚胎表型和纤毛结构进行了检查。为了研究LARP 6调控纤毛发生的分子机制，我们采用RT-PCR和整体原位杂交（whole mount in situ hybridization，WISH）方法检测了在纤毛发生中起重要作用的纤毛相关基因的表达水平。我们敲低了非洲爪蟾胚胎中的LARP 6，发现了神经管闭合缺陷。LARP 6突变体，其损害胶原合成，可以挽救这些缺陷。神经管闭合缺陷与神经管中纤毛（具有运动或感觉相关功能的触角样细胞器）的缺乏一致。在LARP 6变形体中也观察到表皮处没有纤毛，并且这种缺陷是由于没有由中心粒形成并且纤毛组装所需的基体。在多纤毛细胞（MCC）分化过程中，微杀剂，激活纤毛发生过程中中心粒形成所需的基因的转录，可以部分恢复LARP 6变形体中的MCC。此外，LARP 6可能以Notch非依赖性方式控制mcidas的表达。La相关蛋白6通过控制包括mcidas在内的纤毛相关基因的表达，参与纤毛细胞在发育过程中的分化。该LARP 6功能涉及一种机制，该机制与其在结合胶原mRNA和调节其翻译中的既定作用不同。本文的在线版本（doi：10.1186/s13630-017-0047-7）包含补充材料，可供授权用户使用。
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. To 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). We 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. La-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. The online version of this article (doi:10.1186/s13630-017-0047-7) contains supplementary material, which is available to authorized users.