Faculty Opinions recommendation of Activation of PARP-1 by snoRNAs Controls Ribosome Biogenesis and Cell Growth via the RNA Helicase DDX21.

Author(s):  
Holger Bierhoff
2019 ◽  
Vol 75 (6) ◽  
pp. 1270-1285.e14 ◽  
Author(s):  
Dae-Seok Kim ◽  
Cristel V. Camacho ◽  
Anusha Nagari ◽  
Venkat S. Malladi ◽  
Sridevi Challa ◽  
...  

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3571-3584 ◽  
Author(s):  
S. Zaffran ◽  
A. Chartier ◽  
P. Gallant ◽  
M. Astier ◽  
N. Arquier ◽  
...  

This article describes the characterization of a new Drosophila gene that we have called pitchoune (pit) (meaning small in Provence) because mutations in this gene produce larvae that cannot grow beyond the first instar larval stage although they can live as long as 7–10 days. All the tissues are equally affected and the perfectly shaped larvae are indistinguishable from first instar wild-type animals. Analysis of mutant somatic clones suggests a function in cell growth and proliferation, which is supported by the fact that cell proliferation is promoted by pit overexpression. Tagged-Pit, when transfected in S2 cells, localizes mainly to the nucleolus, pointing towards a possible role in ribosome biogenesis and, consequently, in protein biosynthesis. pit encodes a DEAD-box RNA helicase, a family of proteins involved in the control of RNA structure in many cellular processes and its closest homologue is a human DEAD-box RNA helicase, MrDb, whose corresponding gene transcription is directly activated by Myc-Max heterodimers (Grandori, C., Mac, J., Siebelt, F., Ayer, D. E. and Eisenman, R. N. (1996) EMBO J. 15, 4344–4357). The patterns of expression of d-myc and pit are superimposable. Ectopic expression of myc in the nervous system drives an ectopic expression of pit in this tissue indicating that in Drosophila as well, pit is a potential target of d-Myc. These results suggest that myc might promote cell proliferation by activating genes that are required in protein biosynthesis, thus linking cell growth and cell proliferation.


2014 ◽  
Vol 136 (5) ◽  
pp. E272-E281 ◽  
Author(s):  
Marianna Penzo ◽  
Lucia Casoli ◽  
Daniela Pollutri ◽  
Laura Sicuro ◽  
Claudio Ceccarelli ◽  
...  

2020 ◽  
Author(s):  
Xuan Jiang ◽  
Amit Prabhakar ◽  
Stephanie M. Van der Voorn ◽  
Prajakta Ghatpande ◽  
Barbara Celona ◽  
...  

AbstractRibosome biogenesis in eukaryotes requires stoichiometric production and assembly of 80 ribosomal proteins (RPs) and 4 ribosomal RNAs, and its rate must be coordinated with cellular growth. The indispensable regulator of RP biosynthesis is the 5’-terminal oligopyrimidine (TOP) motif, spanning the transcription start site of all RP genes. Here we show that the Microprocessor complex, previously linked to the first step of processing microRNAs (miRNAs), coregulates RP expression by binding the TOP motif of nascent RP mRNAs and stimulating transcription elongation via resolution of DNA/RNA hybrids. Cell growth arrest triggers nuclear export and degradation of the Microprocessor protein Drosha by the E3 ubiquitin ligase Nedd4, accumulation of DNA/RNA hybrids at RP gene loci, decreased RP synthesis, and ribosome deficiency, hence synchronizing ribosome production with cell growth. Conditional deletion of Drosha in erythroid progenitors phenocopies human ribosomopathies, in which ribosomal insufficiency leads to anemia. Outlining a miRNA-independent role of the Microprocessor complex at the interphase between cell growth and ribosome biogenesis offers a new paradigm by which cells alter their protein biosynthetic capacity and cellular metabolism.


2018 ◽  
Vol 64 (6) ◽  
pp. 1205-1213 ◽  
Author(s):  
A. Vizoso-Vázquez ◽  
A. Barreiro-Alonso ◽  
M. I. González-Siso ◽  
E. Rodríguez-Belmonte ◽  
M. Lamas-Maceiras ◽  
...  

RNA ◽  
2019 ◽  
Vol 25 (6) ◽  
pp. 685-701 ◽  
Author(s):  
Franziska M. Boneberg ◽  
Tobias Brandmann ◽  
Lena Kobel ◽  
Jasmin van den Heuvel ◽  
Katja Bargsten ◽  
...  

2011 ◽  
Vol 71 (21) ◽  
pp. 6708-6717 ◽  
Author(s):  
Anthony J. Saporita ◽  
Hsiang-Chun Chang ◽  
Crystal L. Winkeler ◽  
Anthony J. Apicelli ◽  
Raleigh D. Kladney ◽  
...  

2007 ◽  
Vol 404 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Masaya Miyoshi ◽  
Tetsuya Okajima ◽  
Tsukasa Matsuda ◽  
Michiko N. Fukuda ◽  
Daita Nadano

Although bystin has been identified as a protein potentially involved in embryo implantation (a process unique to mammals) in humans, the bystin gene is evolutionarily conserved from yeast to humans. DNA microarray data indicates that bystin is overexpressed in human cancers, suggesting that it promotes cell growth. We undertook RT (reverse transcription)–PCR and immunoblotting, and confirmed that bystin mRNA and protein respectively are expressed in human cancer cell lines, including HeLa. Subcellular fractionation identified bystin protein as nuclear and cytoplasmic, and immunofluorescence showed that nuclear bystin localizes mainly in the nucleolus. Sucrose gradient ultracentrifugation of total cytoplasmic ribosomes revealed preferential association of bystin with the 40S subunit fractions. To analyse its function, bystin expression in cells was suppressed by RNAi (RNA interference). Pulse–chase analysis of ribosomal RNA processing suggested that bystin knockdown delays processing of 18S ribosomal RNA, a component of the 40S subunit. Furthermore, this knockdown significantly inhibited cell proliferation. Our findings suggest that bystin may promote cell proliferation by facilitating ribosome biogenesis, specifically in the production of the 40S subunit. Localization of bystin to the nucleolus, the site of ribosome biogenesis, was blocked by low concentrations of actinomycin D, a reagent that causes nucleolar stress. When bystin was transiently overexpressed in HeLa cells subjected to nucleolar stress, nuclear bystin was included in particles different from the nuclear stress granules induced by heat shock. In contrast, cytoplasmic bystin was barely affected by nucleolar stress. These results suggest that, while bystin may play multiple roles in mammalian cells, a conserved function is to facilitate ribosome biogenesis required for cell growth.


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