The classic molecular-biological narrative has a simple form: Gene-RNA-protein. This is what we learned in school: DNA is transcribed into RNA. In the protein factories (the so-called ribosomes), the RNA serves as a kind of punch card - the proteins are assembled by the machinery exactly according to the DNA template. A single large apparatus can thus produce a wide variety of proteins.
In recent decades, however, biologists have realized that this scheme is far too simple, in particular with regard to the role of RNA. More and more RNA has been found with no code, i.e. no protein instructions. Today, it is assumed that in many living organisms the majority of RNA produced by transcription is actually "non-coding". In humans, noncoding RNA makes up an amazing 98 percent of RNA. Why is so much RNA transcribed that does not serve the "classical" purpose? RNA is obviously not only a DNA blueprint, but also takes on many other tasks in the cell.
But it is not only human biology that continues to pose puzzles. Researchers are particularly interested in trypanosomes, parasitic protozoa responsible for sleeping sickness. These microorganisms are known for their unique molecular biological apparatus. Recently, researchers discovered a particularly unusual mechanism: an ncRNA molecule that acts as a kind of stimulant for ribosomes and that is produced during stress. This finding astonished the researchers because until now only the opposite function of non-coding RNA had been known, acting as inhibitors for the cell apparatus.
During stress, ncRNA molecules attach to ribosomes, pushing the emergency stop button of the protein machinery. When nutrients become scarce or environmental conditions become especially challenging, the entire assembly line is shut down, saving time for the cell. ncRNA molecules are predestined for such a regulatory mechanism - they are produced within fractions of minutes and can thus lead to a much faster reaction of the cell than via the detour of a protein.
But an acceleration of production? This irritated the researchers in two respects: Firstly, it is not immediately clear what the purpose of such a regulation might be, and secondly, it is much more difficult to come up with an intuitive mechanism for such a mode of operation. "We knew of inhibitors, which typically block important binding sites," said the head of the research group.
To unravel the mystery, researchers analyzed the small non-coding RNA (ncRNA) interactome of ribosomes in T. brucei during different growth conditions and life stages. The authors show that the tRNAThr 3´half is produced during nutrient deprivation and becomes one of the most abundant tRNA-derived RNA fragments (tdRs). tRNAThrhalves associate with ribosomes and polysomes and stimulate translation by facilitating mRNA loading during stress recovery once starvation conditions ceased.
Blocking or depleting the endogenous tRNAThr halves mitigates this stimulatory effect both in vivo and in vitro. T. brucei and its close relatives lack the well-described mammalian enzymes for tRNA half processing, thus hinting at a unique tdR biogenesis in these parasites.
Stress situations are usually followed by more "relaxed" times, and being able to produce proteins again as quickly as possible can be crucial. The ncRNA fragment has the effect of bringing the ribosomes up to full production capacity without delay as soon as, for example, sufficient nutrients are available again - to " kick start " the protein production for the cell.
The exact mechanism remains unclear, however, and the group believes this opens up an interesting field for further research. At best, the discovery will lead to a whole new class of substances for the treatment of trypanosomal diseases. For the biological extravagances of trypanosomes also make them vulnerable. Once we understand better how it works, we might find ways to disturb this turbocharger that are completely harmless to humans. The study has been published in Nature Communications.
Non-coding RNA promotes gene expression after stress
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