In order to create proteins, the protein-coding gene must be transcribed into RNA and in the so-called splicing process interrupting segments are removed to form the correct protein-building instructions. Along with scientists at the Helmholtz Zentrum München and the Technical University of Munich (TUM), the European Molecular Biology Laboratory (EMBL) in Heidelberg and the Centre for Genomic Regulation in Barcelona, we have now discovered how the human U2AF protein enables this process. The results have been published in the July 21 issue of Nature.

Splicing requires the cooperation of different proteins, or splicing factors. One such splicing factor, U2AF, was examined in collaboration with German and Spanish scientists. It consists of two structural units and binds to the RNA close to the intron-exon interface. The spatial structure of the U2AF protein alternates between a closed and an open conformation. A matching RNA sequence in the intron causes the U2AF to favour an open conformation, which activates splicing and leads to the elimination of the intron. The intron’s RNA sequence determines how effectively this conformational change can be stabilized. This shift of balance between the closed and the open form of the U2AF protein occurs through a process of natural selection. we presume that similar shape-shifting mechanisms – balanced between a closed, inactive and an open, active conformation – play an important role in the regulation of many other signal pathways in the cell.