Intrinsically disordered proteins SAID1/2 condensate on SERRATE for dual inhibition of miRNA biogenesis in Arabidopsis.
Intrinsically disordered proteins SAID1/2 condensate on SERRATE for dual inhibition of miRNA biogenesis in Arabidopsis.
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DOI：
10.1073/pnas.2216006120
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发表时间：
2023-04-04
影响因子：
11.1
通讯作者：
Zhang, Xiuren
中科院分区：
文献类型：
--
作者：
Shang, Baoshuan;Wang, Lin;Yan, Xingxing;Li, Yanjun;Li, Changhao;Wu, Chaohua;Wang, Tian;Guo, Xiang;Choi, Suk Won;Zhang, Tianru;Wang, Ziying;Tong, Chun-Yip;Oh, Taerin;Zhang, Xiao;Wang, Zhiye;Peng, Xu;Zhang, Xiuren
在拟南芥中，成千上万的蛋白质编码基因已被注释，但没有指定任何功能或生物学过程。其中两个基因，SAID 1/2，编码本质上无序的蛋白质，并且是假设的牙本质涎磷蛋白样蛋白。SAID 1/2位于真核生物RNA代谢的主要调节因子SE（SERRATE）的调控中心。SAID 1/2作用于从SE劫持pri-miRNAs并抑制微处理器活性，同时促进SE蛋白的磷酸化和降解，导致大多数miRNAs的产生受到抑制。这些生化事件可能发生在体内SAID 1/2-SE浓缩物中。因此，本研究不仅揭示了植物中已知基因家族的功能，而且揭示了植物中miRNA生物合成的一个新的调控层。牙本质内紊乱蛋白SAID 1/2是牙本质涎磷蛋白样蛋白，但其功能尚不清楚。在这里，我们确定SAID 1/2作为SERATE（SE）的负调节因子，SERATE（SE）是miRNA生物发生复合体（微处理器）的核心因子。said 1和said 2的功能丧失双突变体导致了多效性发育缺陷和数千个差异表达的基因，这些基因与se. said 1和said 2也显示微处理器组装增加和microRNA（miRNAs）积累增加。机制上，SAID 1/2促进前mRNA加工4激酶A介导的SE磷酸化，导致其在体内降解。出乎意料的是，SAID 1/2对发夹结构的pri-miRNA具有强结合亲和力，并且可以将它们与SE隔离。此外，SAID 1/2在体外直接抑制微处理器对pri-miRNA的加工。而SAID 1/2没有影响SE亚细胞区室化，蛋白质本身表现出液-液相凝聚，在SE上成核。因此，我们提出SAID 1/2通过劫持pri-miRNA来减少miRNA的产生，以防止微处理器的活动，同时促进SE磷酸化及其在拟南芥中的不稳定性。
Thousands of protein-coding genes have been annotated but not assigned with any function or biological process in Arabidopsis. Two of these genes, SAID1/2, encode intrinsically disordered proteins, and are hypothetic dentin sialophosphoprotein-like proteins. SAID1/2 turn out to be in the regulatory hub of SE (SERRATE), which are the master regulators of RNA metabolism in eukaryotes. SAID1/2 act to hijack pri-miRNAs from SE and inhibit microprocessor activity, whereas promoting phosphorylation and degradation of SE protein, leading to repression of production for a majority of miRNAs. These biochemical events likely take place in SAID1/2-SE condensates in vivo. Thus, this study not only deciphered the functions of poorly understood gene family, but also uncovered a new regulatory layer of miRNA biogenesis in plants. Intrinsically disordered proteins (IDPs) SAID1/2 are hypothetic dentin sialophosphoprotein-like proteins, but their true functions are unknown. Here, we identified SAID1/2 as negative regulators of SERRATE (SE), a core factor in miRNA biogenesis complex (microprocessor). Loss-of-function double mutants of said1; said2 caused pleiotropic developmental defects and thousands of differentially expressed genes that partially overlapped with those in se. said1; said2 also displayed increased assembly of microprocessor and elevated accumulation of microRNAs (miRNAs). Mechanistically, SAID1/2 promote pre-mRNA processing 4 kinase A-mediated phosphorylation of SE, causing its degradation in vivo. Unexpectedly, SAID1/2 have strong binding affinity to hairpin-structured pri-miRNAs and can sequester them from SE. Moreover, SAID1/2 directly inhibit pri-miRNA processing by microprocessor in vitro. Whereas SAID1/2 did not impact SE subcellular compartmentation, the proteins themselves exhibited liquid–liquid phase condensation that is nucleated on SE. Thus, we propose that SAID1/2 reduce miRNA production through hijacking pri-miRNAs to prevent microprocessor activity while promoting SE phosphorylation and its destabilization in Arabidopsis.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1016/j.bbrc.2011.10.126
发表时间：
2011-12-16
影响因子：
3.1
作者：
Fedorova, Olga A.;Moiseeva, Tatiana N.;Barlev, Nickolai A.
通讯作者：
Barlev, Nickolai A.
影响因子：
9.2
作者：
Fang, Yuda;Spector, David L.
通讯作者：
Spector, David L.
影响因子：
14.9
作者：
Raczynska KD;Stepien A;Kierzkowski D;Kalak M;Bajczyk M;McNicol J;Simpson CG;Szweykowska-Kulinska Z;Brown JW;Jarmolowski A
通讯作者：
Jarmolowski A
DOI：
10.1073/pnas.0802493105
发表时间：
2008-06-24
影响因子：
11.1
作者：
Laubinger, Sascha;Sachsenberg, Tirno;Weigel, Detlef
通讯作者：
Weigel, Detlef