RBM14 Modulates Tubulin Acetylation and Regulates Spindle Morphology During Meiotic Maturation in Mouse Oocytes.

Hao Qin,Yang-Yang Li,Yi-Feng Yuan,Yi Qu,Jie Qiao

doi:10.3389/fcell.2021.635728

Abstract

RBM14 is an RNA-binding protein that regulates spindle integrity in mitosis; however, its functions during meiosis are still unclear. In this study, we discovered that RBM14 expression was down-regulated in oocytes from old mice. The RBM14 distribution at different stages of meiosis was explored, while it presents overlapped localization patterns with α-tubulin in MI- and MII-stage oocytes. Treatment of MI-stage oocytes with spindle-perturbing agents revealed that RBM14 was co-localized with microtubules. RBM14 knockdown with RBM14-specific morpholino showed that RBM14-depleted oocytes underwent symmetric division compared to the controls. RBM14 knockdown also resulted in spindle defects and chromosome abnormalities during oocyte maturation, presumably due to α-tubulin hyperacetylation. Co-immunoprecipitation analysis demonstrated that RBM14 is interacted with endogenous α-tubulin in mammalian cells. These findings indicate that RBM14 is an essential modulator of oocyte meiotic maturation by regulating α-tubulin acetylation to affect spindle morphology and chromosome alignment. Consequently, RBM14 represents a potential biomarker of oocyte quality and a novel therapeutic target in women with oocyte maturation failure.

Highlights

In recent decades, there has been a trend toward the postponement of first birth due to a diverse array of influences, including women’s rising education, participation in the labor force, individualization and value changes (Mills et al, 2011)
The subcellular localization was confirmed using two different RNA-binding motif protein 14 (RBM14) antibodies (Supplementary Figure 1). These results suggest that a scarcity of RBM14 protein may be associated with a decline in oocyte quality
The results of the present study showed that RBM14 protein was gradually increased from germinal vesicle (GV)- to metaphase II (MII)-stage mouse oocytes and RBM14 depletion caused spindle abnormalities and deficiencies in chromosome segregation

Summary

Introduction

There has been a trend toward the postponement of first birth due to a diverse array of influences, including women’s rising education, participation in the labor force, individualization and value changes (Mills et al, 2011). The age of women at the birth of their first child has been increasing (Mathews and Hamilton, 2016). Reproductive aging in females results in a progressive decline in both the quantity and the quality of oocytes, which are risk factors for infertility, aneuploidy, and low pregnancy rates (Broekmans et al, 2009). The emergence of assisted reproductive technology (ART) offers hope to couples suffering from infertility, and the proportion of women of advanced maternal age who are seeking ART interventions is increasing (Centers for Disease Control Prevention, 2009, 2019; Shea et al, 2015). There is an unmet clinical need to improve oocyte quality and explore the specific etiopathological mechanisms of oocyte maturation failure to ensure better clinical outcomes following ART procedures.

Methods

Results

Conclusion