Abstract
ABSTRACTLa-related protein 6 (Larp6) is a conserved RNA-binding protein found across eukaryotes that has been suggested to regulate collagen biogenesis, muscle development, ciliogenesis, and various aspects of cell proliferation and migration. Zebrafish have two Larp6 family genes: larp6a and larp6b. Viable and fertile single and double homozygous larp6a and larp6b zygotic mutants revealed no defects in muscle structure, and were indistinguishable from heterozygous or wild-type siblings. However, larp6a mutant females produced eggs with chorions that failed to elevate fully and were fragile. Eggs from larp6b single mutant females showed minor chorion defects, but chorions from eggs laid by larp6a;larp6b double mutant females were more defective than those from larp6a single mutants. Electron microscopy revealed defective chorionogenesis during oocyte development. Despite this, maternal zygotic single and double mutants were viable and fertile. Mass spectrometry analysis provided a description of chorion protein composition and revealed significant reductions in a subset of zona pellucida and lectin-type proteins between wild-type and mutant chorions that paralleled the severity of the phenotype. We conclude that Larp6 proteins are required for normal oocyte development, chorion formation and egg activation.
Highlights
La-related proteins (Larps) are a family of evolutionarily conserved RNA-binding proteins with diverse functions (Maraia et al, 2017)
Larp6a is more similar than Larp6b to tetrapod La-related protein 6 (Larp6) proteins, with around 50% and 30% identity to human LARP6, respectively (Fig. S1)
The pattern of larp6a and larp6b mRNA accumulation in embryos was analysed using whole-mount in situ hybridisation. larp6a mRNA appeared ubiquitous at 128-cell, sphere and 50% epiboly stages, and declined thereafter but remained broadly expressed at 30 and 48 hours post-fertilization in the head, trunk and tail (Fig. 1A)
Summary
La-related proteins (Larps) are a family of evolutionarily conserved RNA-binding proteins with diverse functions (Maraia et al, 2017). La, the founding member of the Larp family, was first discovered as an auto-antigen in individuals with lupus erythromatosis and Sjögren’s syndrome, and genetic variation of LARP1, LARP4A, LARP4B and LARP7 are observed in cancers, the role of LARP6 in human disease is as yet unclear (Maraia et al, 2017). Larp is found in a locus linked to knee injury (Rai et al, 2015). None of these medical connections is individually compelling, understanding the key in vivo function(s) of Larp could shed light on various conditions. To our knowledge, no genetic loss of function analysis has been reported in any vertebrate
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