SNORD88B promotes proliferation and invasion of trophoblast by regulating G3BP1 m6 A modification and alternative splicing.

BACKGROUND: Small nucleolar RNA (snoRNA) has recently been shown to play a key role in different diseases, but how snoRNA works to promote the biological behavior of trophoblast remains unclear. METHODS: The expression of snoRNA in the placental villi of females were detected by RNA-seq and qPCR. RNA immunoprecipitation (RIP), RNA methylation co-immunoprecipitation (Me-RIP), and cell experiments were used to explore the molecular mechanism of SNORD88B in regulating the function of villous trophoblasts. RESULTS: SNORD88B was down-regulated in the placental villi of patients with spontaneous abortion, while the overexpression of SNORD88B could promote the proliferation, invasion, and migration of villous trophoblast cells. Mechanistically, SNORD88B directly binds to m6A methyltransferase METTL14 to regulate the m6A modification of G3BP1 mRNA and enhances its mRNA stability by recruiting the reader IGF2BP2. Besides, SNORD88B also regulates the alternative splicing of pre-G3BP1 by recruiting splicing factors SRSF1 and U2AF1, which ameliorates the expression of its effective transcripts to further promote the expression of G3BP1 protein. CONCLUSIONS: We investigated the functional roles and the underlying regulatory mechanisms of SNORD88B in the enhancement of villous trophoblasts' development and that under-expressed SNORD88B could contribute to the maldevelopment of placental villi, which may be related to spontaneous abortion.