Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, WV, USA.
Undergraduate Program in Biochemistry, West Virginia University, Morgantown, WV, USA.
Commun Biol. 2022 Sep 24;5(1):1011. doi: 10.1038/s42003-022-03990-w.
The Musashi proteins, MSI1 and MSI2, are conserved RNA binding proteins with a role in the maintenance and renewal of stem cells. Contrasting with this role, terminally differentiated photoreceptor cells express high levels of MSI1 and MSI2, pointing to a role for the two proteins in vision. Combined knockout of Msi1 and Msi2 in mature photoreceptor cells abrogated the retinal response to light and caused photoreceptor cell death. In photoreceptor cells the Musashi proteins perform distinct nuclear and cytoplasmic functions. In the nucleus, the Musashi proteins promote splicing of photoreceptor-specific alternative exons. Surprisingly, conserved photoreceptor-specific alternative exons in genes critical for vision proved to be dispensable, raising questions about the selective pressures that lead to their conservation. In the cytoplasm MSI1 and MSI2 activate protein expression. Loss of Msi1 and Msi2 lead to reduction in the levels of multiple proteins including proteins required for vision and photoreceptor survival. The requirement for MSI1 and MSI2 in terminally differentiated photoreceptors alongside their role in stem cells shows that, depending on cellular context, these two proteins can control processes ranging from cell proliferation to sensory perception.
Musashi 蛋白（MSI1 和 MSI2）是 RNA 结合蛋白，在维持和更新干细胞方面具有重要作用。与这一作用相反，终末分化的光感受器细胞表达高水平的 MSI1 和 MSI2，表明这两种蛋白在视觉中发挥作用。在成熟的光感受器细胞中联合敲除 Msi1 和 Msi2 会破坏光感受器对光的反应，并导致光感受器细胞死亡。在光感受器细胞中，Musashi 蛋白具有不同的核质功能。在核内，Musashi 蛋白促进光感受器特异性可变外显子的剪接。令人惊讶的是，对视觉至关重要的基因中的保守的光感受器特异性可变外显子被证明是可有可无的，这引发了对导致其保守的选择压力的质疑。在细胞质中，MSI1 和 MSI2 激活蛋白表达。Msi1 和 Msi2 的缺失导致多种蛋白质水平降低，包括视觉和光感受器存活所需的蛋白质。MSI1 和 MSI2 在终末分化的光感受器中的作用以及它们在干细胞中的作用表明，取决于细胞环境，这两种蛋白可以控制从细胞增殖到感觉感知的各种过程。
