DBIRD, a driving force behind protein diversity

Recently discovered and still poorly described, alternative splicing plays a predominant role in protein diversity of organisms. Researchers from Liège, London and Munich have uncovered a new complex protein, DBIRD, which is involved in the regulation of this process. The results of their work have been published in the journal Nature

Many of us have heard of “splicing” in school or at university. Indeed, this process which has been known for a long time is an integral part of the chapter relating to the transcription of DNA into messenger RNA. As a reminder, splicing occurs when polymerase RNA II has created pre-messenger RNA from single strand DNA corresponding to the gene to be expressed. This pre-messenger RNA is a mosaic of coding sequences, the exons, and non-coding sequences, the introns. In order to obtain a pure messenger RNA ready to be translated into protein, the pre-messenger RNA must be cleansed of the non-coding sequences that it is composed of. In this way the introns are eliminated and the exons are interlinked to form mature messenger RNA, which is called the splicing process.

SplicingUntil quite recently, students were taught that a gene codes for a protein by the intermediary of mature messenger RNA stripped of introns. However, things have changed in the last few years! This is not to say that cells have suddenly changed their way of working but scientists have discovered a mechanism that remained hidden up to this point. It is called alternative splicing. “Alternative splicing does not use the factors involved in normal splicing”, explains Pierre Close, a postdoctoral researcher at the F.R.S.-FNRS in the medical chemistry unit of GIGA directed by Alain Chariot. “It is a mechanism that is still relatively unknown because most of studies concerning this process have only been published over the last two or three years”, he continues. One thing is certain, however, alternative splicing increases protein diversity. In fact when a gene, or rather the pre-messenger RNA emanating from this gene, is subject to alternative splicing, it can, depending on the circumstances, give rise to different mature messenger RNAs and therefore different proteins. Why? Quite simply because alternative splicing does not necessarily cause exclusion of all the introns and inclusion of all the exons in the final RNA molecule. According to poorly understood events one or other of the introns can be kept in the mature messenger RNA and one or other of the exons can be excluded. This is how different proteins are produced, or more precisely, protein isoforms.

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