While studying Parkinson's disease, an international research group led by SISSA scientists in Trieste made a discovery which can improve industrial protein synthesis for therapeutic use. They managed to understand the use of RNA when it is not involved in the protein-coding process: the protein synthesis activity of coding genes can be enhanced, for example, by the activity of the non-coding one called "antisense."
To synthetize proteins, the DNA needs RNA molecules serving as short "transcriptions" of the genetic information. The set of all these RNA molecules is called "transcriptome." In the human transcriptome, along with around 25 thousand sequences of coding RNA (i.e. the sequences involved in the synthesis process), the same number of non-coding RNA sequences can be found. Some of these RNAs are called "antisense" because they are specular to sequences of coding RNA called "sense" (the pairing of a sense and an antisense RNA can be seen as a zip). A study published in the journal Nature, coordinated by a group of SISSA researchers in Trieste, has shown that this particular type of antisense RNA has a strengthening function on the coding activity of the proteins of the corresponding genes.
Very little used to be known of "long, non-codifying" RNA and this new research sheds light on some of these molecules. "We focused on one gene, Uchl1, whose mutations are linked to some hereditary types of Parkinson's disease," stated Stefano Gustincich, Professor at SISSA and coordinator of this research project. "We have seen that the non-coding antisense RNA matched to this gene is made up of two fragments, the real antisense fragment matching with the sense RNA that codifies the protein and the SineB2 sequence. The antisense fragment has the function of a "lock" into which the key of the coding RNA specific for that gene is inserted, while the other one has a stimulating function on protein synthesis."
If you change the antisense fragment with the analogous of another gene, the SineB2 sequence maintains its stimulating function on the new gene.
"This is important," explained Gustincich "because it means that the action of sineB2 could be used to stimulate protein production for therapeutic use -- any protein -- in industrial synthesis processes."
A coding RNA is a molecule that copies the information stored in small DNA fragments (genes). This information is then used to make the new protein. There are different types of non-coding RNA, e.g microRNA and small Interference RNA, known for having an inhibiting effect on the transcription of coding RNA.
- Claudia Carrieri, Laura Cimatti, Marta Biagioli, Anne Beugnet, Silvia Zucchelli, Stefania Fedele, Elisa Pesce, Isidre Ferrer, Licio Collavin, Claudio Santoro, Alistair R. R. Forrest, Piero Carninci, Stefano Biffo, Elia Stupka, Stefano Gustincich. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature, 2012; DOI: 10.1038/nature11508
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