Crucial role of Bysl in mammalian preimplantation development as an integral factor for 40S ribosome biogenesis
Crucial role of Bysl in mammalian preimplantation development as an integral factor for 40S ribosome biogenesis
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DOI：
10.1128/mcb.01908-06
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发表时间：
2007-03-01
影响因子：
5.3
通讯作者：
Iwakura, Yoichiro
中科院分区：
文献类型：
--
作者：
Adachi, Kenjiro;Soeta-Saneyoshi, Chie;Iwakura, Yoichiro
在哺乳动物植入前发育过程中，囊胚的形成是一个独特的发育过程，涉及内细胞团和滋养外胚层之间的谱系分离。为了阐明胚泡形成的分子机制，我们功能性地筛选了一个子集的植入前胚胎相关的转录本，通过使用小干扰RNA（siRNA）和确定Bysl（bystin-like）作为一个必需的基因，这一过程。注射Bysl siRNA的胚胎的发育在胚泡形成之前被阻止，导致滋养外胚层分化缺陷。通过使用附加型短发夹RNA表达载体沉默Bysl抑制胚胎干细胞的增殖。外源表达的荧光蛋白标记的Bysl集中在核仁中，具有弥散的核质分布。此外，通过使用RNA干扰或显性失活突变体的Bysl功能的丧失导致40 S核糖体亚基生物合成的缺陷。这些研究结果提供了证据Bysl作为核糖体生物合成的一个不可或缺的因素的关键作用，并建议一个关键的主动翻译机器上的囊胚形成的依赖。
Blastocyst formation during mammalian preimplantation development is a unique developmental process that involves lineage segregation between the inner cell mass and the trophectoderm. To elucidate the molecular mechanisms underlying blastocyst formation, we have functionally screened a subset of preimplantation embryo-associated transcripts by using small interfering RNA (siRNA) and identified Bysl (bystin-like) as an essential gene for this process. The development of embryos injected with Bysl siRNA was arrested just prior to blastocyst formation, resulting in a defect in trophectoderm differentiation. Silencing of Bysl by using an episomal short hairpin RNA expression vector inhibited proliferation of embryonic stem cells. Exogenously expressed Bysl tagged with a fluorescent protein was concentrated in the nucleolus with a diffuse nucleoplasmic distribution. Furthermore, the loss of Bysl function by using RNA interference or dominant negative mutants caused defects in 40S ribosomal subunit biogenesis. These findings provide evidence for a crucial role of Bysl as an integral factor for ribosome biogenesis and suggest a critical dependence of blastocyst formation on active translation machinery.