RNA结合蛋白Lin28在生殖细胞发育和性成熟过程中的作用

作为一个关键的异时性基因(heterochronic gene)家族成员蛋白,Lin28及其同源分子Lin28B在原始生殖细胞(PGCs)发生、生殖细胞肿瘤(GCTs)恶化和性发育成熟过程中发挥着重要的调控作用。Lin28不但可与let-7 miRNA家族的前体终末环相结合,从而阻断let-7miRNA的成熟过程,而且可诱导let-7前体尿苷化和降解。同时,Lin28也可选择性地结合mRNA靶基因,从而直接刺激该基因的翻译过程。Lin28对于PGCs的发育分化至关重要,其表达在小鼠PGCs发育过程中具有时空限制性,还可通过正、负双向途径调节PGC池内生殖细胞数。LIN28的异常表达可能是恶性GCTs发生的早期信号。Lin28还可能是Oct3/4和Nanog途径的上游调控因子,高度调控精原细胞、胚胎癌细胞的分化状态和正常生殖细胞的发育过程;Lin28B基因与青春期女童乳腺发育、男童变声和阴毛发育以及青春期生长高峰密切相关。

Function of RNA-binding Protein Lin28 in Germ Cell Development and Sex Maturation

As a critical heterochronic gene family protein,RNA-binding protein Lin28 and its homologue Lin28B play an important role in primordial germ cells(PGCs) development,germ cell tumors(GCTs) malignancy and sex maturation.Lin28 binds to the terminal loops of let-7 miRNA precursors,leading to inhibition of let-7 miRNA processing and the induction of uridylation and precursor degradation.Lin28 also selectively binds to the target mRNAs and stimulates their translation.Lin28 is essencial for proper PGCs development and has temporal and spatial expression pattern during PGC development in mouse embryo.Lin28 can both positively and negatively regulate the pool of germ cell numbers.Aberrant expression of LIN28 may be an early lesion in germ cell tumorigenesis.Lin28 regulates the differentiation status of seminorma,embryonal carcinoma likely upsteam of Oct3/4 and Nanog,and is likely to play a related role in normal human germ cell development.In addition,Lin28B gene is associated with earlier breast development in girls,earlier voice breaking and more advanced pubic hair development in boys and faster tempo of height growth in both of them.This review summarizes Lin28-medicated regulation and possible mechanisms on germ cell development and sex maturation.