Science：ncRNA沉默X染色体

　　

生物通报道，Howard Hughes医学院，麻省总医院分子学科和哈佛大学医学院遗传学系的科学家近期找到了哺乳动物生殖细胞在分裂时为了保障X染色体平均分配的机制。相关的成果公布在10月31日的Science上。

 

研究发现哺乳动物为了平均分配X染色体的量，雌性哺乳动物会灭活两条X染色体中的一条来确保。X染色体灭活（XCI）过程首先是Xist表达过程被激活，Xist是一类17-kb的非编码RNA（noncoding RNA，简称ncRNA，存在于X染色体的cis区）。由于科学家们暂时没有分离到与Xist相相互作用的分子，因此Xist灭活X染色体的机制一直是个谜。

 

哈佛大学的科学家发现一种1.6k的ncRNA（RepRNA）可与Xist作用，它们形成Polycomb复合物，该复合物直接作用于靶位PRC2。PRC2来自X染色体的RepA RNA，能与Ezh2结合。

 

研究小组发现，在X染色体的灭活过程中RepA与PRC2是其调控因子，ncRNA是辅助Polycomb 复合物发挥作用的辅助因子。

 

原文摘要：Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome

 

【Abstract】

To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.