Human cell growth regulator Ly-1 antibody reactive homologue accelerates processing of preribosomal RNA.
Ribosome biogenesis is an essential process for cell growth and proliferation and is enhanced in cancer and embryonic stem cells. Mouse Ly-1 antibody reactive clone product (Lyar) is expressed at very high levels in many tumor, leukemia or embryonic stem cells; is a novel nucleolar protein with zinc-finger DNA-binding motifs and is involved in cell growth regulation. However, cellular function of Lyar remains unexplored. Here, we show that human homologue of Lyar (LYAR) accelerates ribosome biogenesis at the level of processing of preribosomal RNA (pre-rRNA). We show that LYAR is excluded from the nucleolus after actinomycin D treatment and is present in preribosomal fraction of the nuclear extract as well as in the fractions with 40S, 60S and 90S sedimentation coefficients. LYAR is required for processing of 47S/45S, 32S, 30S and 21S pre-rRNAs. In addition, we show that over-expression of LYAR increases cell proliferation without affecting the expression of c-Myc or p53. Combined, these results suggest that some rapidly growing cells enhance ribosome biogenesis by increasing the expression of LYAR.
Department of Applied Life Science, United Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Sanbancho 5, Chiyoda-ku, Tokyo, 102-0075, Japan.
Naoki
N
Miyazawa
Harunori
H
Yoshikawa
Satomi
S
Magae
Hideaki
H
Ishikawa
Keiichi
K
Izumikawa
Goro
G
Terukina
Ai
A
Suzuki
Sally
S
Nakamura-Fujiyama
Yutaka
Y
Miura
Toshiya
T
Hayano
Wataru
W
Komatsu
Toshiaki
T
Isobe
Nobuhiro
N
Takahashi
D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000378:metabolism*; D040681:Structural Homology, Protein
D004268:DNA-Binding Proteins; C000592018:LYAR protein, human; C081182:Lyar protein, mouse; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D012322:RNA Precursors; D012335:RNA, Ribosomal; D003609:Dactinomycin