scholarly journals TTP and BRF proteins nucleate processing body formation to silence mRNAs with AU-rich elements

2007 ◽  
Vol 21 (6) ◽  
pp. 719-735 ◽  
Author(s):  
T. M. Franks ◽  
J. Lykke-Andersen
Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chang Yin ◽  
Rakesh C Kukreja

mRNA Processing Body (P-Body) is a specialized cytoplasmic structure that functions as a major site for post-transcriptional and trnanslational repression. Target mRNA is guided into P-Body through base-pairing with its micro-RNA (miRNA), where they further bind to P-Body components such as GW182 and AGO2; thus get retained away from translation machinery or degraded. Our previous study detected an increase of a key component of P-Body, miRNA, in heat-shock (HS) protected hearts. To gain further insights into the protective mechanism, we hypothesized that the miRNA-associated protection is mediated through P-Body formation. This hypothesis was tested by measuring three key components of P-Body, i.e., miRNA (target seeker), GW182 (marker of P-Body, also called GW-Body) and AGO2 (mRNA catalytic enzyme). METHODS : ICR mice were either HS-preconditioned (15 min, 42°C, anal temperature) or kept at room temperature (controls). miRNA and proteins were extracted 2 hour after HS. miRNA induction was verified by RT-PCR. P-Body formation was evaluated by measuring the binding of GW182 and AGO2, using a combination of immunopricipitation and Western blotting techniques. To study the role of miRNA in P-Body formation, identical experiments were also repeated in mice treated with miRNA-1 inhibitor (antisense miRNA-1 with 2′-O-methyl base at every nucleotide). RESULTS : Compared to the control, HS-preconditioning significantly induced miRNA-1 (150 ± 11%, mean ± SEM), miRNA-21 (71 ± 10%) and miRNA-24 (68 ± 14%). GW182 (109 ± 16%) and AGO2 (50 ± 16%) were also increased in the HS-group. More importantly, there was an increase (39 ± 11%) in co-immunopricipitation between GW182 and AGO2 in the HS-group than in the control, indicating more binding of the two key P-Body components. However, this co-immunoprecipitation was significantly reduced (−68 ± 8%) in the mice treated with the miRNA-1 inhibitor after HS. CONCLUSION : The formation of P-Body following HS-preconditioning represents a novel protective pathway against ischemic injury. The pharmaceutical potential of P-Body formation may offer a new strategy in cardiac preconditioning.


Author(s):  
Christopher Frederick Mugler ◽  
Maria Hondele ◽  
Stephanie Heinrich ◽  
Ruchika Sachdev ◽  
Pascal Vallotton ◽  
...  

2013 ◽  
Vol 24 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Tzu-Wei Chuang ◽  
Wei-Lun Chang ◽  
Kuo-Ming Lee ◽  
Woan-Yuh Tarn

The exon-junction complex (EJC) deposited on a newly spliced mRNA plays an important role in subsequent mRNA metabolic events. Here we show that an EJC core heterodimer, Y14/Magoh, specifically associates with mRNA-degradation factors, including the mRNA-decapping complex and exoribonucleases, whereas another core factor, eIF4AIII/MLN51, does not. We also demonstrate that Y14 interacts directly with the decapping factor Dcp2 and the 5′ cap structure of mRNAs via different but overlapping domains and that Y14 inhibits the mRNA-decapping activity of Dcp2 in vitro. Accordingly, overexpression of Y14 prolongs the half-life of a reporter mRNA. Therefore Y14 may function independently of the EJC in preventing mRNA decapping and decay. Furthermore, we observe that depletion of Y14 disrupts the formation of processing bodies, whereas overexpression of a phosphomimetic Y14 considerably increases the number of processing bodies, perhaps by sequestering the mRNA-degradation factors. In conclusion, this report provides unprecedented evidence for a role of Y14 in regulating mRNA degradation and processing body formation and reinforces the influence of phosphorylation of Y14 on its activity in postsplicing mRNA metabolism.


2012 ◽  
Vol 29 (1) ◽  
pp. 80-84
Author(s):  
Bei-xin MO ◽  
Hao YE ◽  
Zhong-hua OU ◽  
Li LIU ◽  
Biao HUANG ◽  
...  

2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 27-27
Author(s):  
Jun Ma ◽  
Matyas Flemr ◽  
Mariano Buffone ◽  
Paula Stein ◽  
Petr Svoboda ◽  
...  

2014 ◽  
Vol 61 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Tomoyuki Araki ◽  
Akio Toh-e ◽  
Yoshiko Kikuchi ◽  
Chihiro K. Watanabe ◽  
Takushi Hachiya ◽  
...  

Author(s):  
A. R. Crooker ◽  
W. G. Kraft ◽  
T. L. Beard ◽  
M. C. Myers

Helicobacter pylori is a microaerophilic, gram-negative bacterium found in the upper gastrointestinal tract of humans. There is strong evidence that H. pylori is important in the etiology of gastritis; the bacterium may also be a major predisposing cause of peptic ulceration. On the gastric mucosa, the organism exists as a spiral form with one to seven sheathed flagella at one (usually) or both poles. Short spirals were seen in the first successful culture of the organism in 1983. In 1984, Marshall and Warren reported a coccoid form in older cultures. Since that time, other workers have observed rod and coccal forms in vitro; coccoid forms predominate in cultures 3-7 days old. We sought to examine the growth cycle of H. pylori in prolonged culture and the mode of coccoid body formation.


1979 ◽  
Vol 42 (02) ◽  
pp. 603-610 ◽  
Author(s):  
J H Adams ◽  
J R A Mitchell

SummaryThe ability of potential anti-thrombotic agents to modify platelet-thrombus formation in injured cerebral arteries in the rabbit was tested. Low doses of heparin were without effect, while higher doses produced variable suppression of white body formation but at the expense of bleeding. Aspirin did not inhibit white body formation but another non-steroid anti-inflammatory agent, flurbiprofen was able to do so, as was the anti-gout agent, sulphinpyrazone. Magnesium salts both topically and parenterally, suppressed thrombus formation and increased the concentration of ADP which was required to initiate thrombus production at minor injury sites.


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