The effect of cellular context on miR-155-mediated gene regulation in four major immune cell types.
The effect of cellular context on miR-155-mediated gene regulation in four major immune cell types.
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DOI：
10.1038/s41590-018-0208-x
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发表时间：
2018-10
影响因子：
30.5
通讯作者：
Rudensky AY
中科院分区：
文献类型：
--
作者：
Hsin JP;Lu Y;Loeb GB;Leslie CS;Rudensky AY
许多microRNAs及其靶mRNAs在不同类型的细胞中共表达。然而，目前尚不清楚它们是以细胞上下文无关的方式还是依赖于细胞的方式进行调控。在这里，我们探索了miR-155的转录组靶向和基因调控，其激活诱导的表达在先天性免疫和获得性免疫中发挥着重要作用。通过使用差异iCLIP定位miR-155靶点，使用RNA-Seq定量mRNA，以及使用多聚腺苷酸化(PolyA)-Seq对激活的miR-155充足和缺乏的巨噬细胞、树突状细胞、T和B淋巴细胞进行3‘UTR利用分析，我们发现了许多与miR-155差异结合的靶点。虽然交替切割和聚腺苷酸化(APA)有助于miR-155与某些转录本的不同结合，但在大多数情况下，相同的3‘UTR亚型在不同细胞类型之间受到不同的调控，表明APA不依赖和细胞上下文依赖的miR-155介导的基因调控。我们的研究提供了miR-155调控网络的全面图谱，并为剖析关键免疫细胞类型中上下文依赖和独立的miRNA介导的基因调控提供了宝贵的资源。
Numerous microRNAs and their target mRNAs are co-expressed across diverse cell types. However, it is unknown whether they are regulated in a cellular context-independent or -dependent manner. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets using differential iCLIP, mRNA quantification with RNA-Seq, and 3′UTR usage analysis using polyadenylation (polyA)-Seq in activated miR-155-sufficient and -deficient macrophages, dendritic cells, T and B lymphocytes, we identified numerous targets differentially bound by miR-155. While alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in a majority of cases identical 3′UTR isoforms were differentially regulated across cell types, suggesting ApA-independent and cellular context-dependent miR-155-mediated gene regulation. Our study provides comprehensive maps of miR-155 regulatory networks and offers a valuable resource for dissecting context-dependent and -independent miRNA-mediated gene regulation in key immune cell types.
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影响因子：
7
作者：
Erhard F;Haas J;Lieber D;Malterer G;Jaskiewicz L;Zavolan M;Dölken L;Zimmer R
通讯作者：
Zimmer R
影响因子：
7
作者：
Hausser J;Syed AP;Bilen B;Zavolan M
通讯作者：
Zavolan M
影响因子：
4.8
作者：
Huppertz, Ina;Attig, Jan;D'Ambrogio, Andrea;Easton, Laura E.;Sibley, Christopher R.;Sugimoto, Yoichiro;Tajnik, Mojca;Koenig, Julian;Ule, Jernej
通讯作者：
Ule, Jernej
影响因子：
10.5
作者：
Ke S;Alemu EA;Mertens C;Gantman EC;Fak JJ;Mele A;Haripal B;Zucker-Scharff I;Moore MJ;Park CY;Vågbø CB;Kusśnierczyk A;Klungland A;Darnell JE Jr;Darnell RB
通讯作者：
Darnell RB
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