Sequential waves of polyadenylation and deadenylation define a translation circuit that drives meiotic progression

2008 ◽  
Vol 36 (4) ◽  
pp. 665-670 ◽  
Author(s):  
Eulàlia Belloc ◽  
Maria Piqué ◽  
Raúl Méndez

The maternal mRNAs that drive meiotic progression in oocytes contain short poly(A) tails and it is only when these tails are elongated that translation takes place. Cytoplasmic polyadenylation requires two elements in the 3′-UTR (3′-untranslated region), the hexanucleotide AAUAAA and the CPE (cytoplasmic polyadenylation element), which also participates in the transport and localization, in a quiescent state, of its targets. However, not all CPE-containing mRNAs are activated at the same time during the cell cycle, and polyadenylation is temporally and spatially regulated during meiosis. We have recently deciphered a combinatorial code that can be used to qualitatively and quantitatively predict the translational behaviour of CPE-containing mRNAs. This code defines positive and negative feedback loops that generate waves of polyadenylation and deadenylation, creating a circuit of mRNA-specific translational regulation that drives meiotic progression.

2007 ◽  
Vol 293 (1) ◽  
pp. R83-R98 ◽  
Author(s):  
A. Peters ◽  
M. Conrad ◽  
C. Hubold ◽  
U. Schweiger ◽  
B. Fischer ◽  
...  

Feedback control, both negative and positive, is a fundamental feature of biological systems. Some of these systems strive to achieve a state of equilibrium or “homeostasis”. The major endocrine systems are regulated by negative feedback, a process believed to maintain hormonal levels within a relatively narrow range. Positive feedback is often thought to have a destabilizing effect. Here, we present a “principle of homeostasis,” which makes use of both positive and negative feedback loops. To test the hypothesis that this homeostatic concept is valid for the regulation of cortisol, we assessed experimental data in humans with different conditions (gender, obesity, endocrine disorders, medication) and analyzed these data by a novel computational approach. We showed that all obtained data sets were in agreement with the presented concept of homeostasis in the hypothalamus-pituitary-adrenal axis. According to this concept, a homeostatic system can stabilize itself with the help of a positive feedback loop. The brain mineralocorticoid and glucocorticoid receptors—with their known characteristics—fulfill the key functions in the homeostatic concept: binding cortisol with high and low affinities, acting in opposing manners, and mediating feedback effects on cortisol. This study supports the interaction between positive and negative feedback loops in the hypothalamus-pituitary-adrenal system and in this way sheds new light on the function of dual receptor regulation. Current knowledge suggests that this principle of homeostasis could also apply to other biological systems.


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