Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation.
Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation.
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DOI：
10.1038/s41467-018-06184-3
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发表时间：
2018-09-19
影响因子：
16.6
通讯作者：
Heissmeyer V
中科院分区：
文献类型：
--
作者：
Essig K;Kronbeck N;Guimaraes JC;Lohs C;Schlundt A;Hoffmann A;Behrens G;Brenner S;Kowalska J;Lopez-Rodriguez C;Jemielity J;Holtmann H;Reiche K;Hackermüller J;Sattler M;Zavolan M;Heissmeyer V
RNA结合蛋白Roquin-1和Roquin-2冗余地控制基因表达和细胞命运决定。在这里，我们证明了Roquin不仅与茎环结构相互作用，而且还与大约一半的靶标中存在的线性序列元件相互作用。对Nfkbid3‘-UTR的一个最小反应元件的综合分析表明，六个茎环结构相互协作，实施强大而深刻的转录后调控。只有多个Roquin蛋白与几个茎环结合才能施加完全抑制，这一过程包括去烯化和去封端，但也包括翻译抑制。在全球范围内，大多数Roquin靶标都受到mRNA衰退的调控，而包括NFAT5 mRNA在内的一小部分在其3‘-UTRs中有更多结合位点的基因也受到翻译抑制。这些发现为Roquin介导的调控的稳健性和幅度如何在复杂的顺式元件中编码提供了洞察力。已知Roquin靶标包含两种类型的序列结构基序，即构成性和选择性衰变元素(CDE和ADE)。在这里，作者描述了一个线性Roquin结合元件(LBE)，也参与目标识别，并表明Roquin结合影响靶向mRNAs子集的翻译。
The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem–loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3′-UTR shows that six stem–loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem–loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition. Globally, most Roquin targets are regulated by mRNA decay, whereas a small subset, including the Nfat5 mRNA, with more binding sites in their 3′-UTRs, are also subject to translational inhibition. These findings provide insights into how the robustness and magnitude of Roquin-mediated regulation is encoded in complex cis-elements. Roquin targets are known to contain two types of sequence-structure motifs, the constitutive and the alternative decay elements (CDE and ADE). Here, the authors describe a linear Roquin binding element (LBE) also involved in target recognition, and show that Roquin binding affects the translation of a subset of targeted mRNAs.
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影响因子：
14.9
作者：
Kowalska J;Wypijewska del Nogal A;Darzynkiewicz ZM;Buck J;Nicola C;Kuhn AN;Lukaszewicz M;Zuberek J;Strenkowska M;Ziemniak M;Maciejczyk M;Bojarska E;Rhoads RE;Darzynkiewicz E;Sahin U;Jemielity J
通讯作者：
Jemielity J
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
3.7
作者：
Kobayashi S;Hara A;Isagawa T;Manabe I;Takeda K;MaruYama T
通讯作者：
MaruYama T
影响因子：
4.5
作者：
Kowalska, Joanna;Lewdorowicz, Magdalena;Jemielity, Jacek
通讯作者：
Jemielity, Jacek
影响因子：
4.8
作者：
Hafner, Markus;Renwick, Neil;Farazi, Thalia A.;Mihailovic, Aleksandra;Pena, John T. G.;Tuschl, Thomas
通讯作者：
Tuschl, Thomas