https://scholars.lib.ntu.edu.tw/handle/123456789/416744
標題: | The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression | 作者: | Pan, W.-A. HSIN-YUE TSAI Wang, S.-C. MING-YEN HSIAO PEI-YUAN WU Tsai, M.-D. |
關鍵字: | cell cycle; Ki67; ribosome biogenesis; nucleolar stress; RNA recognition motif | 公開日期: | 2015 | 出版社: | TAYLOR & FRANCIS INC | 卷: | 12 | 期: | 3 | 起(迄)頁: | 255 | 來源出版物: | RNA Biology | 摘要: | © Wen-An Pan, Hsin-Yue Tsai, Shun-Chang Wang, Michael Hsiao, Pei-Yu Wu, and Ming-Daw Tsai. Ribosome biogenesis governs protein synthesis. NIFK is transactivated by c-Myc, the key regulator of ribosome biogenesis. The biological function of human NIFK is not well established, except that it has been shown to interact with Ki67 and NPM1. Here we report that NIFK is required for cell cycle progression and participates in the ribosome biogenesis via its RNA recognition motif (RRM). We show that silencing of NIFK inhibits cell proliferation through a reversible p53-dependent G1 arrest, possibly by induction of the RPL5/RPL11-mediated nucleolar stress. Mechanistically it is the consequence of impaired maturation of 28S and 5.8S rRNA resulting from inefficient cleavage of internal transcribed spacer (ITS) 1, a critical step in the separation of pre-ribosome to small and large subunits. Complementation of NIFK silencing by mutants shows that RNA-binding ability of RRM is essential for the pre-rRNA processing and G1 progression. More specifically, we validate that the RRM of NIFK preferentially binds to the 5'-region of ITS2 rRNA likely in both sequence specific and secondary structure dependent manners. Our results show how NIFK is involved in cell cycle progression through RRM-dependent pre-rRNA maturation, which could enhance our understanding of the function of NIFK in cell proliferation, and potentially also cancer and ribosomopathies. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84928226282&partnerID=MN8TOARS https://scholars.lib.ntu.edu.tw/handle/123456789/416744 |
ISSN: | 1547-6286 1555-8584 |
DOI: | 10.1080/15476286.2015.1017221 18887868 |
SDG/關鍵字: | internal transcribed spacer; Myc protein; NIFK protein; protein; protein p53; ribosome protein; ribosome RNA; RNA 28S; RNA 5.8S; unclassified drug; MKI67IP protein, human; nuclear protein; protein binding; protein p53; ribosomal spacer DNA; RNA 28S; RNA 5.8S; RNA precursor; signal peptide; small interfering RNA; Article; binding affinity; biogenesis; cell cycle G1 phase; cell cycle progression; cell proliferation; cell separation; cell stress; controlled study; DNA cleavage; G1 phase cell cycle checkpoint; gene silencing; genetic complementation; human; human cell; molecular recognition; mutant; nucleolus; protein motif; protein RNA binding; protein secondary structure; protein synthesis; ribosome; RNA processing; RNA recognition motif; RNA sequence; amino acid sequence; antagonists and inhibitors; binding site; conformation; cytology; genetics; metabolism; molecular genetics; nucleotide motif; osteoblast; protein synthesis; sequence alignment; signal transduction; transcription initiation; tumor cell line; Amino Acid Sequence; Binding Sites; Cell Line, Tumor; Cell Proliferation; DNA, Ribosomal Spacer; G1 Phase Cell Cycle Checkpoints; Humans; Intracellular Signaling Peptides and Proteins; Molecular Sequence Data; Nuclear Proteins; Nucleic Acid Conformation; Nucleotide Motifs; Osteoblasts; Protein Binding; Protein Biosynthesis; Ribosomes; RNA Precursors; RNA, Ribosomal, 28S; RNA, Ribosomal, 5.8S; RNA, Small Interfering; Sequence Alignment; Signal Transduction; Transcriptional Activation; Tumor Suppressor Protein p53 |
顯示於: | 分子醫學研究所 |
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