The Regulation Mechanism of RNA splicing Was Revealed
RNA splicing is a very complicated process which is carried out by spliceosome. Our spliceosomes are assembled from protein and RNA molecules, including 170 different proteins and five "small nuclear RNAs" (snRNAs). Currently we believed that certain snRNAs represent the tools with which the spliceosome carries out the cutting and joining of RNA sections, turning the "pre?mRNA" into mature messenger RNA with “alternative splicing”. The proteins of the spliceosome are needed to bring these tools to the right place at the right time, and to set them into operation. Thus the process is well regulated.
For every splicing step, a new spliceosome is assembled on the pre?mRNA molecule. The cutting of the pre?RNA won’t start before identifying the target splicing site. The snRNAs are brought into position, but first in an inactive form as they are packed into other components of the spliceosome. On receiving a particular "start signal," the molecular become active. Until now, we only know that protein Brr2 was responsible for activating.
Brr2 belongs to a family of enzymes—"RNA helicases" due to their ability to separate RNA molecules that are paired with one another. In this way Brr2 sets free an snRNA "knife" and allows it to do its job. However, Brr2 also possesses a remarkable molecular architecture to distinguish it from other helicases. Until recent it was not known how this special architecture is put to use in the cell to regulate the function of Brr2.
But now the mechanism is uncovered via biochemical studies. In the study, the helicase activity of Brr2 is inhibited by a particular part of another protein—Prp8. In follow up, they identified the atomic structure of the Brr2 protein in contact with the relevant regulatory portion of Prp8 by means of X?ray crystallography. By doing this, the structure was clearly presented: at the end of the Prp8 molecule there is an elongated region of protein that blocks a central channel of the Brr2 helicase and, by doing so, prevents the RNA molecules that are separated by Brr2 from binding to the helicase.
Further they confirmed that changes in Prp8 impair its function as a regulator of Brr2. Moreover, the mechanism above described is not the only way. The researchers found an additional regulatory mechanism that controls the Brr2 helicase. Another region of the protein Prp8 binds to the RNA molecules that are to be separated from one another by Brr2, and, by doing so, snatches them away from the enzyme. The various mechanisms stress the importance of the exact timing of the process.
Next, the researchers plan to investigate whether the regulation of Brr2 might also play a part in "alternative splicing.
Article Link: The Regulation Mechanism of RNA splicing Was Revealed
Tags: Enzymes, Protein, crystallography, RNA splicing
