Involvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts

Article


Moraleva, A., Magoulas, B., Polzikov, M., Hacot, S., Mertani, H., Diaz, J. and Zatsepina, O. 2017. Involvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts. Cell Cycle. 16 (20), pp. 1979-1991. https://doi.org/10.1080/15384101.2017.1371880
TypeArticle
TitleInvolvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts
AuthorsMoraleva, A., Magoulas, B., Polzikov, M., Hacot, S., Mertani, H., Diaz, J. and Zatsepina, O.
Abstract

The nucleolar proteins which link cell proliferation to ribosome biogenesis are regarded to be potentially oncogenic. Here, in order to examine the involvement of an evolutionary conserved nucleolar protein SURF6/Rrp14 in proliferation and ribosome biogenesis in mammalian cells, we established stably transfected mouse NIH/3T3 fibroblasts capable of conditional overexpression of the protein. Cell proliferation was monitored in real-time, and various cell cycle parameters were quantified based on flow cytometry, Br-dU-labeling and conventional microscopy data. We show that overexpression of SURF6 accelerates cell proliferation and promotes transition through all cell cycle phases. The most prominent SURF6 pro-proliferative effects include a significant reduction of the population doubling time, from 19.8±0.7 to 16.2±0.5 hours (t-test, p<0.001), and of the length of cell division cycle, from 17.6±0.6 to 14.0±0.4 hours (t-test, p<0.001). The later was due to the shortening of all cell cycle phases but the length of G1 period was reduced most, from 5.7 ±0.4 to 3.8 ±0.3 hours, or by ∼30%, (t-test, p<0.05). By Northern blots and qRT-PCR, we further showed that the acceleration of cell proliferation was concomitant with an accumulation of rRNA species along both ribosomal subunit maturation pathways. It is evident, therefore, that like the yeast homologue Rrp14, mammalian SURF6 is involved in various steps of rRNA processing during ribosome biogenesis. We concluded that SURF6 is a novel positive regulator of proliferation and G1/S transition in mammals, implicating that SURF6 is a potential oncogenic protein, which can be further studied as a putative target in anti-cancer therapy.

Keywordsnucleolus; SURF6; SURF6 cell cycle; proliferation; ribosome biogenesis; rRNA processing; mouse NIH; 3T3 fibroblasts
LanguageEnglish
PublisherInforma UK Limited
JournalCell Cycle
ISSN1538-4101
Electronic1551-4005
Publication dates
Online05 Sep 2017
Print18 Oct 2017
Publication process dates
Deposited12 Sep 2017
Accepted19 Aug 2017
Output statusPublished
Accepted author manuscript
Copyright Statement

This is an Accepted Manuscript of an article published by Taylor & Francis in Cell Cycle on 05/09/2017, available online: http://www.tandfonline.com/10.1080/15384101.2017.1371880

Digital Object Identifier (DOI)https://doi.org/10.1080/15384101.2017.1371880
Web of Science identifierWOS:000414094300018
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