La-related Protein 6 Controls Ciliated Cell Differentiation

Overview

Journal Cilia

Publisher Biomed Central

Specialty Cell Biology

Date 2017 Mar 28

PMID 28344782

Citations 6

Authors

Zarko Manojlovic

Ryan Earwood

Akiko Kato

Diana Perez

Oscar A Cabrera

Ruth Didier

Timothy L Megraw

Branko Stefanovic

Yoichi Kato

Affiliations

Soon will be listed here.

Abstract

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 in 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).

Results: We knocked down LARP6 in 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 in 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 including . This LARP6 function involves a mechanism that is distinct from its established role in binding to collagen mRNAs and regulating their translation.

Citing Articles

Genome-wide investigation of the LARP gene family: focus on functional identification and transcriptome profiling of ZmLARP6c1 in maize pollen.

Xiang X, Deng Q, Zheng Y, He Y, Ji D, Vejlupkova Z BMC Plant Biol. 2024; 24(1):348.

PMID: 38684961 PMC: 11057080. DOI: 10.1186/s12870-024-05054-z.

Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry.

Manojlovic Z, Auslander A, Jin Y, Schmidt R, Xu Y, Chang S Genes (Basel). 2023; 14(3).

PMID: 36980938 PMC: 10048728. DOI: 10.3390/genes14030665.

LARP6C orchestrates posttranscriptional reprogramming of gene expression during hydration to promote pollen tube guidance.

Billey E, Hafidh S, Cruz-Gallardo I, Litholdo C, Jean V, Carpentier M Plant Cell. 2021; 33(8):2637-2661.

PMID: 34124761 PMC: 8408461. DOI: 10.1093/plcell/koab131.

Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development.

Sheel A, Shao R, Brown C, Johnson J, Hamilton A, Sun D Front Cell Dev Biol. 2020; 8:622.

PMID: 32850788 PMC: 7405549. DOI: 10.3389/fcell.2020.00622.

Maternal Larp6 controls oocyte development, chorion formation and elevation.

Hau H, Ogundele O, Hibbert A, Monfries C, Exelby K, Wood N Development. 2020; 147(4).

PMID: 32054660 PMC: 7055395. DOI: 10.1242/dev.187385.

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