scholarly journals Telomerase exerts physiological and tumor promoting functions by stimulating ribosomal biogenesis

2015 ◽  
Keyword(s):  
2012 ◽  
Vol 23 (1) ◽  
pp. 22-35 ◽  
Author(s):  
Barbara Widmann ◽  
Franziska Wandrey ◽  
Lukas Badertscher ◽  
Emanuel Wyler ◽  
Jens Pfannstiel ◽  
...  

RIO proteins form a conserved family of atypical protein kinases. Humans possess three distinct RIO kinases—hRio1, hRio2, and hRio3, of which only hRio2 has been characterized with respect to its role in ribosomal biogenesis. Here we show that both hRio1 and hRio3, like hRio2, are associated with precursors of 40S ribosomal subunits in human cells. Furthermore, we demonstrate that depletion of hRio1 by RNA interference affects the last step of 18S rRNA maturation and causes defects in the recycling of several trans-acting factors (hEnp1, hRio2, hLtv1, hDim2/PNO1, and hNob1) from pre-40S subunits in the cytoplasm. Although the effects of hRio1 and hRio2 depletion are similar, we show that the two kinases are not fully interchangeable. Moreover, rescue experiments with a kinase-dead mutant of hRio1 revealed that the kinase activity of hRio1 is essential for the recycling of the endonuclease hNob1 and its binding partner hDim2 from cytoplasmic pre-40S. Kinase-dead hRio1 is trapped on pre-40S particles containing hDim2 and hNob1 but devoid of hEnp1, hLtv1, and hRio2. These data reveal a role of hRio1 in the final stages of cytoplasmic pre-40S maturation.


2016 ◽  
Vol 27 (20) ◽  
pp. 3031-3039 ◽  
Author(s):  
Michael W. Woellhaf ◽  
Frederik Sommer ◽  
Michael Schroda ◽  
Johannes M. Herrmann

Whereas the structure and function of cytosolic ribosomes are well characterized, we only have a limited understanding of the mitochondrial translation apparatus. Using SILAC-based proteomic profiling, we identified 13 proteins that cofractionated with the mitochondrial ribosome, most of which play a role in translation or ribosomal biogenesis. One of these proteins is a homologue of the bacterial ribosome-silencing factor (Rsf). This protein is generated from the composite precursor protein Atp25 upon internal cleavage by the matrix processing peptidase MPP, and in this respect, it differs from all other characterized mitochondrial proteins of baker’s yeast. We observed that cytosolic expression of Rsf, but not of noncleaved Atp25 protein, is toxic. Our results suggest that eukaryotic cells face the challenge of avoiding negative interference from the biogenesis of their two distinct translation machineries.


2017 ◽  
Vol 292 (24) ◽  
pp. 10306-10315 ◽  
Author(s):  
Jia-Lin Wang ◽  
Tusar T. Saha ◽  
Yang Zhang ◽  
Changyu Zhang ◽  
Alexander S. Raikhel

2010 ◽  
Vol 285 (33) ◽  
pp. 25812-25821 ◽  
Author(s):  
Xiao-Xin Sun ◽  
Yue-Gang Wang ◽  
Dimitris P. Xirodimas ◽  
Mu-Shui Dai

2017 ◽  
Vol 108 ◽  
pp. 106-113 ◽  
Author(s):  
Shihao Zhao ◽  
Yunlong Xia ◽  
Fuyang Zhang ◽  
Zhenyu Xiong ◽  
Yueyang Li ◽  
...  
Keyword(s):  

2017 ◽  
Vol 642 ◽  
pp. 153-157 ◽  
Author(s):  
Ewa Kilanczyk ◽  
Kariena R. Andres ◽  
Justin Hallgren ◽  
Sujata Saraswat Ohri ◽  
Marikki Laiho ◽  
...  

2020 ◽  
Vol 62 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Tanner C. Korponay ◽  
Joseph Balnis ◽  
Catherine E. Vincent ◽  
Diane V. Singer ◽  
Amit Chopra ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Yanfang Wang ◽  
Shan Xin ◽  
Kai Zhang ◽  
Run Shi ◽  
Xuanwen Bao

Introduction. Gliomas are infiltrative neoplasms of a highly invasive nature. Different stages of gliomas feature distinct genomic, genetic, and epigenetic changes. The long noncoding RNA Growth Arrest Specific Transcript 5 (GAS5) is an identified tumour suppressor involved in several cancers. However, the underlying roles of the GAS5 gene in lower-grade glioma (LGG) patients are not clear. Methods. Via bioinformatic analysis based on TCGA-LGG and TCGA-GBM data, we explored the mechanisms of GAS5 expression in LGG (grades II and III) and high-grade glioma (glioblastoma multiforme, grade IV). The log-rank test and multivariate Cox analysis were performed to find the association between GAS5 and overall survival (OS) in LGG patients. Weighted gene coexpression network analysis (WGCNA) and RNA-Seq analysis were applied to find the key gene network associated with GAS5. Results. We found that GAS5 expression was downregulated in both LGG and glioblastoma multiforme (GBM) compared with normal brain tissue. Low methylation in the GAS5 promoter region was detected in both LGG and GBM tissues. The amplification type was the predominant type of GAS5 gene alteration in both LGG and GBM. High GAS5 expression was more associated with long overall survival (OS) in LGG patients than in GBM patients. The multivariate survival analysis of GAS5 and clinical and molecular characteristics in LGG patients further confirmed the association between GAS5 and OS in LGG patients. We then developed a nomogram for clinical use. WGCNA and RNA-Seq analysis indicated that ribosomal biogenesis and translation initiation were the predominant events regulated by GAS5 in LGG patients. Conclusion. Taken together, these results demonstrate that GAS5 expression is associated with OS in LGG patients and that its underlying roles involve the regulation of ribosomal biogenesis and translation initiation, which may aid in identifying a new target for the treatment of LGG.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jennifer E. Cowan ◽  
Justin Malin ◽  
Yongge Zhao ◽  
Mina O. Seedhom ◽  
Christelle Harly ◽  
...  

AbstractInteractions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size.


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