A Tudor Domain Protein SPINDLIN1 Interacts with the mRNA-Binding Protein SERBP1 and Is Involved in Mouse Oocyte Meiotic Resumption

Abstract

Mammalian oocytes are arrested at prophase I of meiosis, and resume meiosis prior to ovulation. Coordination of meiotic arrest and resumption is partly dependent on the post-transcriptional regulation of maternal transcripts. Here, we report that, SPINDLIN1 (SPIN1), a maternal protein containing Tudor-like domains, interacts with a known mRNA-binding protein SERBP1, and is involved in regulating maternal transcripts to control meiotic resumption. Mouse oocytes deficient for Spin1 undergo normal folliculogenesis, but are defective in resuming meiosis. SPIN1, via its Tudor-like domain, forms a ribonucleoprotein complex with SERBP1, and regulating mRNA stability and/or translation. The mRNA for the cAMP-degrading enzyme, PDE3A, is reduced in Spin1 mutant oocytes, possibly contributing to meiotic arrest. Our study demonstrates that Spin1 regulates maternal transcripts post-transcriptionally and is involved in meiotic resumption.

The Tudor Domain Protein Spindlin1 Is Involved in Intrinsic Antiviral Defense against Incoming Hepatitis B Virus and Herpes Simplex Virus Type 1

“…In oocyte, Spindlin1 interacts and cooperates with SERBP1 to regulate mRNA stability [26]. Our data show that Spindlin1 does not modulate HBV RNA stability but acts mainly at the level of HBV transcription.…”

Developing Spindlin1 small-molecule inhibitors by using protein microarrays

“…The interaction of SPIN1 with H3K4me3 is stabilized when a second Tudor domain engages the H3R8me2a mark 28 . SPIN1 null mice exhibit early post-natal lethality and display a defect in meiosis 41 . Finally, SPIN1 promotes RET signaling in liposarcoma 40 , where it was found that: 1) knockdown of SPIN1 in a liposarcoma cell line (T778) reduces cell proliferation, 2) proliferation rates are rescued with wild-type SPIN1, but not with a mutant in the Tudor domain that binds H3K4me3 (the interaction we are targeting), and 3) SPIN1 knockdown dramatically reduces tumor weight in a xenograft mouse model.…”

The histone code reader SPIN1 controls RET signaling in liposarcoma

“…The protein belongs to the SPIN/SSTY family implicated in cell cycle regulation during gametogenesis and the transition between gamete and embryo [2, 3]. Furthermore, SPIN1 was reported to be highly expressed in several types of tumors [4], and ectopic expression in cell lines was observed to affect cell cycle, chromatin segregation, or to induce apoptosis, cellular transformation, or tumor formation in nude mice [5–8].…”