The mouse Sry locus harbors a cryptic exon that is essential for male sex determination
The mouse Sry locus harbors a cryptic exon that is essential for male sex determination
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DOI：
10.1126/science.abb6430
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发表时间：
2020-10-02
期刊：
影响因子：
56.9
通讯作者：
Tachibana, Makoto
中科院分区：
文献类型：
--
作者：
Miyawaki, Shingo;Kuroki, Shunsuke;Tachibana, Makoto
哺乳动物性别决定基因Sry诱导雄性发育。自30年前发现以来，Sry一直被认为是一个单外显子基因。在这里，我们确定了一个神秘的第二外显子的小鼠Sry和相应的两个外显子类型的Sry（Sry-T）转录。缺乏Sry-T的XY小鼠发生性逆转，并且在XX小鼠中异位表达Sry-T诱导雄性发育。SRY-T信使RNA的表达类似于典型的单外显子类型Sry（SRY-S），但SRY-T蛋白主要表达是因为SRY-S的C末端缺少降解决定子。Sry外显子2似乎最近在小鼠中通过获得逆转录转座子衍生的编码序列来取代降解决定子而进化。我们的研究结果表明，在自然界中，SRY-T，而不是SRY-S，是真正的睾丸决定因素。
The mammalian sex-determining gene Sry induces male development. Since its discovery 30 years ago, Sry has been believed to be a single-exon gene. Here, we identified a cryptic second exon of mouse Sry and a corresponding two-exon type Sry (Sry-T) transcript. XY mice lacking Sry-T were sex-reversed, and ectopic expression of Sry-T in XX mice induced male development. Sry-T messenger RNA is expressed similarly to that of canonical single-exon type Sry (Sry-S), but SRY-T protein is expressed predominantly because of the absence of a degron in the C terminus of SRY-S. Sry exon2 appears to have evolved recently in mice through acquisition of a retrotransposon-derived coding sequence to replace the degron. Our findings suggest that in nature, SRY-T, not SRY-S, is the bona fide testis-determining factor.