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Nuclear receptors are ligand‐regulated transcription factors that play important role in regulating insect metamorphosis through the ecdysone signalling pathway. In this study, we investigated the nuclear receptor HR38 gene in Bombyx mori (BmHR38), belonging to the NR4A subfamily. BmHR38 mRNA was highly expressed in the head and epidermis at the pupal stage. The expression of the BmHR38 gene was influenced by different doses of 20E at different times. A BmHR38 deletion mutant silkworm was generated using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system. Compared with the wild‐type B. mori, the BmHR38 deletion mutant resulted in abnormal development during the pupal stage, leading to either failed eclosion or the formation of abnormal adult wings. After silencing of BmHR38 in the pupal stage, the phenotype of pupa or moth had no significant change, but it did result in reduced egg production. The mRNA levels of USP, E75 and E74 were significantly increased, while the transcript levels of FTZ‐F1 were suppressed after RNA interference. Furthermore, interference with BmHR38 also inhibited the expressions of chitin metabolism genes, including Chs1, Chs2, Chi, Chi‐h and CDA. Our results suggest that BmHR38 is essential for pupal development and pupa–adult metamorphosis in B. mori by regulating the expression of NRs and chitin metabolism genes. [ABSTRACT FROM AUTHOR]

Simple Summary: Nucleases are highly diverse enzymes that cleave phosphodiester bonds of nucleic acids with highly diverse enzymes. A widespread superfamily of nucleases contains PIN-like domains, which are identified in eukaryotes and prokaryotes. The domesticated silkworm Bombyx mori, as a lepidoptera model insect, has numerous advantages in life science and can be used as an important model in various research areas. However, few nucleases on RNA insensitivity or virus defense have been studied in B. mori. In this study, we identified a protein asteroid (BmAst) in silkworm B. mori, containing the PIN domain and XPG domain. BmAst gene was highest expressed in hemocytes and fat body of the 5th larvae. The BmAst gene expression was significantly induced by Bombyx mori nucleopolyhedrovirus (BmNPV) or dsRNA. By interference with BmAst gene expression, the proliferation of BmNPV in B. mori was significantly increased, whereas the survival rate of silkworm larvae was significantly lower when compared with the control. Our results indicate that BmAst is involved in silkworm resistance to BmNPV infection. Nuclease is a type of protein that degrades nucleic acids, which plays an important role in biological processes, including RNA interference efficiency and antiviral immunity. However, no evidence of a link between nuclease and Bombyx mori nucleopolyhedrovirus (BmNPV) infection in silkworm B. mori has been found. In this study, a protein asteroid (BmAst) containing the PIN domain and XPG domain was identified in silkworm B. mori. BmAst gene was highest expressed in hemocytes and fat body of the 5th instar larvae, and high expression in the pupa stage. The transcriptional levels of the BmAst gene in 5th instar larvae were significantly induced by BmNPV or dsRNA. After knocking down BmAst gene expression by specific dsRNA, the proliferation of BmNPV in B. mori was increased significantly, whereas the survival rate of larvae was significantly lower when compared with the control. Our findings indicate that BmAst is involved in silkworm resistance to BmNPV infection. [ABSTRACT FROM AUTHOR]