Structural investigation of the SF3b complex

Pre-mRNA splicing is an essential step of gene expression in which the non-coding introns are removed and the coding exons are ligated to form a mature mRNA. An adenosine from the so-called branch point sequence (BPS) provides the reactive group for the first chemical step of splicing. The splicing process occurs on the spliceosome, a multi- Megadaltons molecular machinery which assembles stepwise from five small nuclear ribonucleoprotein particles (snRNPs) and numerous non-snRNP proteins. The so-called SF3b complex is one main building block of the U2 snRNP and the regulator of several stages during the splicing cycle. Thus, the SF3b is involved in the proper recognition of the BPS, the formation of the catalytic center and thepositioning of the BPS adenosine inside the catalytic center. It is composed of six conserved proteins (Rse1, Hsh155, Cus1, Hsh49, Rds3, Ysf3) and, according to cryo-EM reconstruction, SF3b have the shape of a closed bivalve with a inner cavity. In addition to its importance for the splicing mechanism, various connections between SF3b proteins and very diverse human diseases have been evidenced in the last years (e. g. genetic disorder, viral infections with HIV, and various types of cancers).