Friday, December 23, 2016

When in stress, cell's quality control stringency is relaxed.

All forms of life on our planet have endured relentless variations in their environment which led to their modification and subsequent selection. Each generation goes through imperceptible course of endless natural selection. At any given time an organism seems to be at equilibrium with its environment. It is just a matter of little nudge and the organism's emergency beacons are activated. When faced with a life threatening situation, an organism is bound to protect itself even at the cost of damage to itself, provided the damage is lethal. It is because the prize in evolution is survival and reproduction. Something similar is observable at a cellular level. In a normal condition a cell goes by its usual business of transcribing RNA from the DNA inside the nucleus. As all the cellular processes these pathways are regulated. The DNA, RNA and proteins are all subjected to stringent quality control mechanisms whereby defective ones are identified and degraded to prevent malfunction inside the cell.
mRNA passing through nuclear pore complex
(source: Lawrence Berkeley National Laboratory)

When stress arrives, for example :- increase in temperature then the cell has to select between two extremes, first, to consume standard time and energy so that all the stringent quality control mechanisms are followed? or choose survival by removing those extra 'check-posts' and continue by paying the cost of error. The cells removes these 'check-post' , lowers the bar for quality control, so that immediate emergency systems are in place before its too late. Under heat stress heat shock proteins act as a chaperone which assist in folding of other proteins. As increase in temperature is adverse to protein folding, these heat shock proteins comes to rescue and helps endure the stressful phase. 

During these times of stress, cell's emergency system prioritizes the transcription of heat shock genes while all other genes are stopped immediately. The mechanism by which cell selects heat shock transcript from the normal one has largely remained elusive. Now a study by Zander et al. has found a mechanism by which S cerevisiae achieves this. 

Normally, when a transcription is takin place certain adapter proteins are loaded oton transcribing RNA. These adapter protein recruit export receptors which assist in transportation of mRNA to from the nucleus to the cytoplasm. But under temperature stress, heat shock transcripts (mRNA) bypass the need of adapter proteins on the transcribing mRNA and directly binds to Mex67 export signal protein. Hsf a transcription factor was observed to assist the loading of export proteins onto these transcripts. Without any delay, this quick maneuver helps cell quickly fulfills the demand of heat shock proteins inside the cytoplasm. Broad theme which emerges from this study is that only export+adapter+mRNA undergo quality control mechanism. The group engineered the heat shock promoter to regular mRNA of normal gene and they observed similarly relaxed quality control as for heat shock proteins. 

Although heat shock transcripts are error prone but its quick delivery into the cytoplasm without any delay, allows cell to survive under extreme stress conditions. It's no wonder that emergency systems like this and broad range of mechanisms to escape unwanted situations have made life flourish on this planet.

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