SLERT Regulates DDX21 Rings Associated with Pol I Transcription
SLERT Regulates DDX21 Rings Associated with Pol I Transcription
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SLERT 调节与 Pol I 转录相关的 DDX21 环。
DOI：
10.1016/j.cell.2017.04.011
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发表时间：
2017-05-04
期刊：
影响因子：
64.5
通讯作者：
Chen, Ling-Ling
中科院分区：
文献类型：
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作者：
Xing, Yu-Hang;Yao, Run-Wen;Chen, Ling-Ling
RNA聚合酶I(Pol I)合成rRNA的失调与细胞增殖失控有关。在这里，我们报告了一种盒H/ACA小核仁RNA(SnoRNA)末端的长非编码RNA(LncRNA)，它能增强Pre-rRNA转录(SLERT)。SLERT需要盒H/ACA snoRNAs在两端进行生物发生和向核仁的转位。SLERT的缺失会损害Pre-rRNA转录和rRNA的产生，导致肿瘤发生的减少。在机制上，SLERT通过143个核苷酸的非snoRNA序列与DEAD-box RNA解旋酶DDX21相互作用。超分辨图像显示，DDX21在多个Pol I复合体周围形成环状结构，并抑制前rRNA转录。SLERT的结合变构改变了单个DDX21分子，松开了DDX21环，并驱逐了DDX21对Pol I转录的抑制。综上所述，我们的结果揭示了SLERT InncRNA对核糖体生物发生的重要控制及其在作用于Pol I络合物的DDX21环状排列中的调节作用。
Dysregulated rRNA synthesis by RNA polymerase I (Pol I) is associated with uncontrolled cell proliferation. Here, we report a box H/ACA small nucleolar RNA (snoRNA)-ended long noncoding RNA (lncRNA) that enhances pre-rRNA transcription (SLERT). SLERT requires box H/ACA snoRNAs at both ends for its biogenesis and translocation to the nucleolus. Deletion of SLERT impairs pre-rRNA transcription and rRNA production, leading to decreased tumorigenesis. Mechanistically, SLERT interacts with DEAD-box RNA helicase DDX21 via a 143-nt non-snoRNA sequence. Super-resolution images reveal that DDX21 forms ring-shaped structures surrounding multiple Pol I complexes and suppresses pre-rRNA transcription. Binding by SLERT allosterically alters individual DDX21 molecules, loosens the DDX21 ring, and evicts DDX21 suppression on Pol I transcription. Together, our results reveal an important control of ribosome biogenesis by SLERT lncRNA and its regulatory role in DDX21 ring-shaped arrangements acting on Pol I complexes.