RNA结合蛋白PTB在精子发生中的研究进展

RNA-binding protein PTB in spermatogenesis: Progress in studies

RNA结合蛋白通过与新生转录子相互作用来调节细胞的功能,因而在人体发育和内环境中越来越受到关注。多聚嘧啶序列结合蛋白(PTB)家族是RNA结合蛋白的重要组成部分,且在基因表达的转录后调控中起到至关重要的作用。随着对PTB转录后调控以及各个亚型的深入研究发现,在精子发生过程中,Ptbp1(polypyrimidine tract-binding protein 1)在精原细胞有丝分裂中为主要表达亚型,而Ptbp2在精母细胞减数分裂期至精子细胞阶段中大量表达,且能与磷酸甘油酸激酶2(PGK2)mRNA 3'端非编码区结合,从而使Pgk2 mRNA在小鼠生殖细胞中稳定表达。当睾丸组织中Ptbp2表达失活时,生精小管中生精细胞分化停滞在圆形精子细胞阶段并伴有大量的巨型多核细胞(MNCs)产生,精母细胞凋亡增加,生精小管变细,精子成熟障碍,进而影响男性生育能力。本文就PTB的结构及其在精子发生中的调控作用进行综述。

RNA binding proteins （RBPs） regulate the function of cells by interacting with nascent transcripts and therefore are receiving increasing attention fronl researchers for their roles in tissue development and homeostasis. The polypyrimidine tract binding （PTB） protein family of RBPs are important posttranscriptional regulators of gene expression. Further investigations on the post-tran- seriptional regulation mechanisms and isoforms of PTB proteins in the spermatogenesis show that PTB protein 1 （ Ptbpl ） is a predomi- nant isoform in mitotic cells （spermatogonia） , while Ptbp2 predominates in meiotic spermatocytes and postmeiotic spermatids and binds to the specific 3＂untranslated region （3＂UTR） of the phosphoglycerate kinase 2 （Pgk-2） mRNA, which helps to stabilize Pgk-2 mRNA in male mouse germ ceils. In case of Ptbp2 inactivation in the testis, the differentiation of germ cells arrests in the stage of round spcr- matids, with proliferation of multinucleated ceils in the seminiferous tubule, increased apoptosis of spermatocytes, atrophy of seminiferous tubules, and lack of elongating spermatids, which consequently affects male fertility. This article presents an overview on the structure of the PTB protein and its role in regulating mammalian spermatogenesis.