He Xiyi, Zhang Yunfei, Mao Zenghui, Liu Gang, Huang Lihua, Liu Xiaowen, Su Yuyan, Xing Xiaowei
Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Aug 6;56(11):1673-1686. doi: 10.3724/abbs.2024134.
, a testis-specific gene, is associated with acephalic spermatozoa syndrome (ASS). Here, we demonstrate that SUN5 is involved in mRNA export. In -knockout mice ( 5 ), poly(A) RNA accumulates in the nuclei of germ cells, leading to reduced sperm counts, decreased sperm motility and disrupted sperm head-to-tail junctions. Additionally, in the GC-2 germ cell line with RNA interference of , heterogeneous nuclear ribonucleoproteins (hnRNPs) and poly (A) RNA (mainly mRNA) are retained in the nucleus. Further mechanistic studies reveal that SUN5 interacts with Nxf1 (nuclear RNA export factor 1) and nucleoporin 93 (Nup93). Interference with Nup93 inhibits mRNA export. Treatment with leptomycin B to block the CRM1 pathway indicates that regulates mRNA export through an Nxf1-dependent pathway. In mice, the binding of Nxf1 and Nup93 decreases due to loss of Sun5 function, and the process of submitting Nxf1-binding mRNPs to Nup93 is inhibited, resulting in abnormal spermatogenesis. Together, these data may elucidate a novel pathway for mRNA export in male germ cells.
一种睾丸特异性基因与无头精子综合征(ASS)相关。在此,我们证明SUN5参与mRNA输出。在SUN5基因敲除小鼠(Sun5 -/-)中,多聚腺苷酸(poly(A))RNA在生殖细胞的细胞核中积累,导致精子数量减少、精子活力下降以及精子头尾连接破坏。此外,在对SUN5进行RNA干扰的GC - 2生殖细胞系中,核不均一核糖核蛋白(hnRNPs)和多聚腺苷酸(poly(A))RNA(主要是mRNA)滞留在细胞核中。进一步的机制研究表明,SUN5与Nxf1(核RNA输出因子1)和核孔蛋白93(Nup93)相互作用。干扰Nup93会抑制mRNA输出。用雷帕霉素B处理以阻断CRM1途径表明,SUN5通过Nxf1依赖的途径调节mRNA输出。在Sun5 -/-小鼠中,由于Sun5功能丧失,Nxf1和Nup93的结合减少,并且将与Nxf1结合的核蛋白体颗粒(mRNPs)提交给Nup93的过程受到抑制,导致精子发生异常。总之,这些数据可能阐明了雄性生殖细胞中mRNA输出的一条新途径。