SCD6 induces ribonucleoprotein granule formation in trypanosomes in a translation-independent manner, regulated by its Lsm and RGG domains.
SCD6 induces ribonucleoprotein granule formation in trypanosomes in a translation-independent manner, regulated by its Lsm and RGG domains.
复制标题
DOI：
10.1091/mbc.e13-01-0068
复制
发表时间：
2013-07
影响因子：
3.3
通讯作者：
Kramer S
中科院分区：
文献类型：
--
作者：
Krüger T;Hofweber M;Kramer S
锥虫缺乏在酵母和人类中鉴定的核糖核蛋白（RNP）颗粒的许多核心组分（例如，DCP 1/2）。这项研究提供的证据表明，SCD 6是锥虫中的核心RNP颗粒成分：过表达诱导颗粒独立于翻译，甚至当SCD 6靶向细胞核。颗粒类型和颗粒数量取决于RGG结构域。核糖核蛋白（RNP）颗粒是由RNA和蛋白质组成的细胞质内显微镜下可见的结构，在mRNA的降解和储存中发挥作用。锥虫具有几种类型的RNP颗粒，但缺乏酵母和人类中鉴定的大多数颗粒核心组分。例外的是SCD 6/Rap 55，它是加工体（P-体）形成所必需的。在这项研究中，我们分析了锥虫SCD 6在RNP颗粒形成中的作用。在过度表达时，大多数SCD 6聚集成在核周边富集的多个颗粒，其募集P体和应激颗粒蛋白以及mRNA。颗粒蛋白质组成取决于颗粒到核的距离。与酵母和人类中的发现相反，颗粒形成与翻译抑制无关，并且也可以在SCD 6的核靶向后在核中发生。虽然单独的SCD 6 Lsm结构域对于颗粒诱导是必要的和足够的，但RGG基序决定颗粒类型和数量：缺少完整的RGG基序导致形成较少的类似于P体的颗粒。颗粒数量的差异仍然核靶向后，表明不依赖于功能的RGG域。我们建议，在锥虫，局部增加SCD 6浓度可能足以通过招募mRNA诱导颗粒。选择性结合到SCD 6的RGG和/或Lsm结构域的蛋白质可能负责调节颗粒类型和数量。
Trypanosomes lack many core components of ribonucleoprotein (RNP) granules identified in yeast and humans (e.g., DCP1/2). This study provides evidence for SCD6 being the core RNP granule component in trypanosomes: overexpression induces granules independent of translation, and even when SCD6 is targeted to the nucleus. Granule type and granule number are dependent on the RGG domain. Ribonucleoprotein (RNP) granules are cytoplasmic, microscopically visible structures composed of RNA and protein with proposed functions in mRNA decay and storage. Trypanosomes have several types of RNP granules, but lack most of the granule core components identified in yeast and humans. The exception is SCD6/Rap55, which is essential for processing body (P-body) formation. In this study, we analyzed the role of trypanosome SCD6 in RNP granule formation. Upon overexpression, the majority of SCD6 aggregates to multiple granules enriched at the nuclear periphery that recruit both P-body and stress granule proteins, as well as mRNAs. Granule protein composition depends on granule distance to the nucleus. In contrast to findings in yeast and humans, granule formation does not correlate with translational repression and can also take place in the nucleus after nuclear targeting of SCD6. While the SCD6 Lsm domain alone is both necessary and sufficient for granule induction, the RGG motif determines granule type and number: the absence of an intact RGG motif results in the formation of fewer granules that resemble P-bodies. The differences in granule number remain after nuclear targeting, indicating translation-independent functions of the RGG domain. We propose that, in trypanosomes, a local increase in SCD6 concentration may be sufficient to induce granules by recruiting mRNA. Proteins that bind selectively to the RGG and/or Lsm domain of SCD6 could be responsible for regulating granule type and number.