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Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of PRMT1 with an extra N-terminal sequence and brain-specific expression. We use zebrafish ( Danio rerio ) as a vertebrate model to study PRMT8 function and putative redundancy with PRMT1. The transcripts of zebrafish  prmt8  were specifically expressed in adult zebrafish brain and ubiquitously expressed from zygotic to early segmentation stage before the neuronal development. Whole-mount  in situ  hybridization revealed ubiquitous  prmt8  expression pattern during early embryonic stages, similar to that of  prmt1.  Knockdown of  prmt8  with antisense morpholino oligonucleotide phenocopied  prmt1- knockdown, with convergence/extension defects at gastrulation. Other abnormalities observed later include short body axis, curled tails, small and malformed brain and eyes. Catalytically inactive  prmt8  failed to complement the morphants, indicating the importance of methyltransferase activity. Full-length  prmt8  but not  prmt1  cRNA can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with the N-terminus of Prmt8 can rescue the  prmt8  morphants. In contrast, N-terminus- deleted but not full-length  prmt8  cRNA can rescue the  prmt1  morphants as efficiently as  prmt1  cRNA. Abnormal brain morphologies illustrated with brain markers and loss of fluorescent neurons in a transgenic fish upon  prmt8  knockdown confirm the critical roles of  prmt8  in neural development. In summery, our study is the first report showing the expression and function of  prmt8  in early zebrafish embryogenesis. Our results indicate that  prmt8  may play important roles non-overlapping with  prmt1  in embryonic and neural development depending on its specific N-terminus.

The Critical Role of Protein Arginine Methyltransferase prmt8 in Zebrafish Embryonic and Neural Development Is Non-Redundant with Its Paralogue prmt1