Category Archives: Translation

When timing matters

Biochemistry, Cell physiology, Circadian Clock, Drug, Translation

When you are an endocrinologist you know that hormones are released into the circulation in pulses and that melatonin is only produced in the dark, that glucocortoids concentrations in the blood are high during the night and low during the day, that many hormones have their rhythm. Every hormone has its time, as the prophet sayed.

However, what has not been known until now is that to the same extend more than 40 % of all genes are expressed in a circadian (day long) rhythm.  Zhang and colleagues measured in the mouse ( and the might be the only shortcoming of the study ) the gene expression with arrays to determine many gene simultaneously in every hour of the day and night. They found 43 % of all genes expressed in a circadian rhythm. They also determined noncoding RNAs  and found 1000 of them cycling.

There are consequences for medicine and therapy: The targets of the top most drugs are expressed all in (specific) rhythms: When a drug like aspirin for example is taken at the wrong time, it would be gone before the target is fully expressed. The scale of this problem seems tremendous. Any pharmaceutical company has to do its home work again. But on the other hand, therapy might become more reliable which would be a large improvement.

The circadian rhythm in the 12 organs analysed are quite different. It might take some time to get used to the thinking that genes in question are not stable during the day but change the level of expression. It will be interesting to follow the aftermath of that paper. The paper is open access and therefore free to everybody.

A must.

 

A StAR is everywhere!

Biochemistry, Endocrinology, Translation,

Steriod acute regulator protein (StAR) is the protein involved in the time-limiting step of stereogenesis since one molecule StAR must be produced to transport one molecule cholesterol  from the cell membrane to the mitochondrium. There, the side-chain cleavage enzyme converts the cholesterol to pregnenolone to begin the steroid synthesis for androgens and estrogens, mineralocorticoids and cortisols. StAR is therefore an important molecule for the Endocrinologist. Whereever StAR is expressed, steroids are supposed to be made. Its characteristic structure – a pocket to acquire just one molecule of cholesterol – has been crystallized and determined by X-ray spectrometry. What is much less known that it has homologues throughout the animal kingdom, even other taxa share the structure which is thus fairly old and that is used not only for cholesterol, but for numerous lipids, too.

Strange enough, a molecule which is at the beginning of a specialized reaction chain such as steroidogenesis is widely used. Sometimes the introduction to an article is an eye-opener: In Current Biology the paper by Schrick shows just such a case. They are concerned with StAR homologues in the plant Arabidopsis and their role as transcription factors. Maybe not so interesting to the general audience, but the introduction resumes the role of StAR and StAR-like proteins fairly well. Recommended.

Translation Errors – not so bad at all

Biochemistry, Cell physiology, Translation, Translational error

Faithfull translation of mRNA into proteins  is one of the hallmarks of life. It is generally accepted that any deviation from this pathway leads to missformed proteins and is considered deleterious per se.

A very enlightning review in Trends in Biological Sciences (TIBS; DOI: 10.1016/j.tibs.2014.06.002) shows that errors in translation are dealt with in a productive way. First of all mistranslation are obviously regulated due to species and environnement which is by itself showing that mistranslation is beneficial for the organism, at least part of it. Furthermore mistranslation is well tolerated and not deleterious for the organism. Different organisms have evolved strategies to deal with it. It seems clear that by mistranslation the organism generates alternative proteins which may help to adapt the different environmental challenges.

Recommended!