HASTY moves to chromatin for miRNA production.
HASTY moves to chromatin for miRNA production.
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HASTY转移到染色质中产生miRNA。
DOI：
10.1016/j.molp.2021.01.012
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发表时间：
2021-03-01
期刊：
影响因子：
27.5
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Sun D;Zhang X
自20世纪90年代微RNA（microRNAs，miRNAs）被发现以来，其在真核生物中的生物学过程中发挥着重要的调控作用。miRNAs的工厂位于细胞核内，而它们的工作场所是细胞质。因此，miRNA从细胞核到细胞质的迅速转运对于它们的适当功能是必不可少的。在后生动物中，该承诺由输出蛋白5（EXP 5/XPO 5），即miRNA前体（premiRNA）的核输出蛋白进行（Yi et al.，2003年）。在植物中，HASTY（HST），一种穿梭于细胞核和细胞质之间的核转运蛋白家族成员，已被鉴定为miRNA途径中的组分（Park，et al.，2005年）。由于HST是哺乳动物EXP 5/XPO 5的直系同源物，因此该蛋白质一直被模糊地假定为植物miRNA的输出者。然而，一个有争议的观察结果是，尽管在hst突变体中它们的总体稳态水平降低，但miRNA在细胞核和细胞质之间的亚细胞分布没有改变（Park等人，2005年）。此外，已经显示AGO 1（植物RNA沉默中的主效应子）移动到细胞核中以摄取miRNA，并且随后返回到细胞质以通过EXPORTIN 1（EXPO 1/CRM 1）发挥功能（Bologna et al.，2018），并且AGO 1-miRNA复合物的运输由核孔蛋白1（NUP 1）/转录偶联的输出2复合物（TREX-2）促进（Zhang等人，2020年）。这些报道也挑战了HST作为miRNA输出者的功能。Cambiagno et al.（2020），最近发表在分子植物，解决了长期的谜团，并证明HST编排的转录和加工的主要底物的miRNA（pri-miRNAs），而不是作为一个出口的miRNA之前认为（图1）.Cambiagno和同事们开始解决这个问题，通过询问是否HST的输出功能是必不可少的，它在miRNA通路中的作用.核转运蛋白通常与小GTP酶RAN合作进行细胞转运。类似地，HST通过其N-末端结构域与GTP酶RAN 1 -3相互作用以获得潜在的输出活性。Cambiagno及其同事没有观察到相对于Col-0，在ran单突变体或双突变体中测试的miRNA的稳态积累或核/胞质比率的任何变化。与ran突变体类似，表达N-末端结构域缺失的HST（hst/HST DN）的互补转化体未显示miRNA的亚细胞分布的变化。然而，与hst本身类似，hst; HST DN具有降低的miRNA水平。因此，最初的结果使作者得出结论，HST通过其N-末端结构域正向调节miRNA积累，并且该功能可以与HST输出活性解偶联。接下来，Cambiagno及其同事评估了不同背景下HST截短形式的亚细胞定位。全长HST显示RAN 1的核/质比增加，与RAN 1在HST穿梭中的作用一致。令人惊讶的是，不与RAN蛋白相互作用的HST DN在Col-0中显示出减少的细胞核/细胞质分布。对比细胞
MicroRNAs (miRNAs) have been well appreciated for their critical roles in regulating various biological processes in eukaryotes since the initial discovery of these tiny molecules in 1990s. The factory for miRNAs is located inside the nucleus, whereas their workplace is the cytoplasm. Thus, the prompt transport of miRNAs from nucleus to cytoplasm is essential for their proper functionality. In metazoans, the commitment is carried out by Exportin 5 (EXP5/XPO5), the nuclear exporter of miRNA precursors (premiRNAs)(Yi et al., 2003). In plants, HASTY (HST), a karyopherin family member that shuttles between nucleus and cytoplasm, has been identified as a component in the miRNA pathway (Park, et al., 2005). Since HST is an ortholog of mammalian EXP5/XPO5, the protein has been ambiguously assumed to act as an exporter of plant miRNAs. However, a controversial observation is that the subcellular distribution of miRNAs between nucleus and cytoplasm is not altered, despite the decrease in their overall steady-state levels in the hst mutants (Park et al., 2005). Furthermore, it has been shown that AGO1, a master effector in plant RNA silencing, moves into nucleus to uptake miRNAs and subsequently returns to cytoplasm for functions via EXPORTIN1 (EXPO1/CRM1)(Bologna et al., 2018), and that the trafficking of AGO1-miRNA complexes is promoted by Nucleoporin 1 (NUP1)/Transcription-coupled Export 2 complex (TREX-2)(Zhang et al., 2020). These reports also challenged HST function as a miRNA exporter. An excellent study by Cambiagno et al.(2020), recently published in Molecular Plant, solved the long-term mystery and demonstrated that HST orchestrates the transcription and processing of primary substrates of miRNAs (pri-miRNAs), rather than serving as an exporter for miRNAs as previously thought (Figure 1).Cambiagno and colleagues began to address the issue by asking whether the exporting function of HST is essential for its role in the miRNA pathway. Karyopherins typically conduct cellular transport in cooperation with the small GTPases RANs. Similarly, HST, through its N-terminal domain, interacts with the GTPases RAN1–3 for the potential exporting activity. Cambiagno and colleagues did not observe any change in the steady-state accumulation or nuclear/cytoplasmic ratios of tested miRNAs in ran single or double mutants relative to Col-0. Similar to ran mutants, complementation transformants expressing N-terminal domain depleted HST (hst/HST DN) did not show a change in subcellular distribution of miRNAs. However, hst; HST DN harbored, similar to hst itself, reduced levels of miRNAs. Hence, the initial results led the authors to conclude that HST positively regulates miRNA accumulation via its N-terminal domain and this function can be uncoupled from HST exporting activity. Next, Cambiagno and colleagues assessed subcellular localizations of HST truncation forms in different backgrounds. Full length HST displayed an increased nucleus/cytoplasm ratio in ran1, consistent with the proposed role of RAN1 in the HST shuttling. Surprisingly, HST DN, which does not interact with RAN proteins, displayed a decreased nucleus/cytoplasm distribution in Col-0. The contrasted cellular
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影响因子：
10.5
作者：
Yi, R;Qin, Y;Cullen, BR
通讯作者：
Cullen, BR
DOI：
10.1073/pnas.1619755114
发表时间：
2017-04-11
影响因子：
11.1
作者：
Zhang, Zhonghui;Guo, Xinwei;Zhang, Xiuren
通讯作者：
Zhang, Xiuren
影响因子：
27.5
作者：
Cambiagno, Damian A.;Giudicatti, Axel J.;Manavella, Pablo A.
通讯作者：
Manavella, Pablo A.
DOI：
10.1073/pnas.0405570102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Park, MY;Wu, G;Poethig, RS
通讯作者：
Poethig, RS
影响因子：
18
作者：
Zhang, Bailong;You, Chenjiang;Chen, Xuemei
通讯作者：
Chen, Xuemei