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SLERT Regulates DDX21 Rings Associated with Pol I Transcription

2017; Cell Press; Volume: 169; Issue: 4 Linguagem: Inglês

10.1016/j.cell.2017.04.011

1097-4172

Yu‐Hang Xing, Run-Wen Yao, Yang Zhang, Chunjie Guo, Shan Jiang, Guang Xu, Rui Dong, Li Yang, Ling‐Ling Chen,

Cancer-related molecular mechanisms research

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.