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1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation.
PLoS One 2010; 5(12):e14244Plos

Abstract

BACKGROUND

Ribosome biogenesis is required for protein synthesis and cell proliferation. Ribosome subunits are assembled in the nucleolus following transcription of a 47S ribosome RNA precursor by RNA polymerase I and rRNA processing to produce mature 18S, 28S and 5.8S rRNAs. The 18S rRNA is incorporated into the ribosomal small subunit, whereas the 28S and 5.8S rRNAs are incorporated into the ribosomal large subunit. Pol I transcription and rRNA processing are coordinated processes and this coordination has been demonstrated to be mediated by a subset of U3 proteins known as t-UTPs. Up to date, five t-UTPs have been identified in humans but the mechanism(s) that function in the t-UTP(s) activation of Pol I remain unknown. In this study we have identified 1A6/DRIM, which was identified as UTP20 in our previous study, as a t-UTP. In the present study, we investigated the function and mechanism of 1A6/DRIM in Pol I transcription.

METHODOLOGY/PRINCIPAL FINDINGS

Knockdown of 1A6/DRIM by siRNA resulted in a decreased 47S pre-rRNA level as determined by Northern blotting. Ectopic expression of 1A6/DRIM activated and knockdown of 1A6/DRIM inhibited the human rDNA promoter as evaluated with luciferase reporter. Chromatin immunoprecipitation (ChIP) experiments showed that 1A6/DRIM bound UBF and the rDNA promoter. Re-ChIP assay showed that 1A6/DRIM interacts with UBF at the rDNA promoter. Immunoprecipitation confirmed the interaction between 1A6/DRIM and the nucleolar acetyl-transferase hALP. It is of note that knockdown of 1A6/DRIM dramatically inhibited UBF acetylation. A finding of significance was that 1A6/DRIM depletion, as a kind of nucleolar stress, caused an increase in p53 level and inhibited cell proliferation by arresting cells at G1.

CONCLUSIONS

We identify 1A6/DRIM as a novel t-UTP. Our results suggest that 1A6/DRIM activates Pol I transcription most likely by associating with both hALP and UBF and thereby affecting the acetylation of UBF.

Authors+Show Affiliations

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21151873

Citation

Peng, Qunhui, et al. "1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation." PloS One, vol. 5, no. 12, 2010, pp. e14244.
Peng Q, Wu J, Zhang Y, et al. 1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation. PLoS ONE. 2010;5(12):e14244.
Peng, Q., Wu, J., Zhang, Y., Liu, Y., Kong, R., Hu, L., ... Ke, Y. (2010). 1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation. PloS One, 5(12), pp. e14244. doi:10.1371/journal.pone.0014244.
Peng Q, et al. 1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation. PLoS ONE. 2010 Dec 7;5(12):e14244. PubMed PMID: 21151873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation. AU - Peng,Qunhui, AU - Wu,Jianguo, AU - Zhang,Ying, AU - Liu,Yun, AU - Kong,Ruirui, AU - Hu,Lelin, AU - Du,Xiaojuan, AU - Ke,Yang, Y1 - 2010/12/07/ PY - 2010/07/23/received PY - 2010/11/18/accepted PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2011/7/6/medline SP - e14244 EP - e14244 JF - PloS one JO - PLoS ONE VL - 5 IS - 12 N2 - BACKGROUND: Ribosome biogenesis is required for protein synthesis and cell proliferation. Ribosome subunits are assembled in the nucleolus following transcription of a 47S ribosome RNA precursor by RNA polymerase I and rRNA processing to produce mature 18S, 28S and 5.8S rRNAs. The 18S rRNA is incorporated into the ribosomal small subunit, whereas the 28S and 5.8S rRNAs are incorporated into the ribosomal large subunit. Pol I transcription and rRNA processing are coordinated processes and this coordination has been demonstrated to be mediated by a subset of U3 proteins known as t-UTPs. Up to date, five t-UTPs have been identified in humans but the mechanism(s) that function in the t-UTP(s) activation of Pol I remain unknown. In this study we have identified 1A6/DRIM, which was identified as UTP20 in our previous study, as a t-UTP. In the present study, we investigated the function and mechanism of 1A6/DRIM in Pol I transcription. METHODOLOGY/PRINCIPAL FINDINGS: Knockdown of 1A6/DRIM by siRNA resulted in a decreased 47S pre-rRNA level as determined by Northern blotting. Ectopic expression of 1A6/DRIM activated and knockdown of 1A6/DRIM inhibited the human rDNA promoter as evaluated with luciferase reporter. Chromatin immunoprecipitation (ChIP) experiments showed that 1A6/DRIM bound UBF and the rDNA promoter. Re-ChIP assay showed that 1A6/DRIM interacts with UBF at the rDNA promoter. Immunoprecipitation confirmed the interaction between 1A6/DRIM and the nucleolar acetyl-transferase hALP. It is of note that knockdown of 1A6/DRIM dramatically inhibited UBF acetylation. A finding of significance was that 1A6/DRIM depletion, as a kind of nucleolar stress, caused an increase in p53 level and inhibited cell proliferation by arresting cells at G1. CONCLUSIONS: We identify 1A6/DRIM as a novel t-UTP. Our results suggest that 1A6/DRIM activates Pol I transcription most likely by associating with both hALP and UBF and thereby affecting the acetylation of UBF. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21151873/1A6/DRIM_a_novel_t_UTP_activates_RNA_polymerase_I_transcription_and_promotes_cell_proliferation_ L2 - http://dx.plos.org/10.1371/journal.pone.0014244 DB - PRIME DP - Unbound Medicine ER -