Pre-mRNA splicing is executed by the ribonucleoprotein machinery spliceosome. Each cycle of pre-mRNA splicing comprises two sequential steps: branching and exon ligation, This cycle is often repeated multiple times for the generation of an eukaryotic mRNA.  The first chemical step results in cleavage of the bond at the beginning of the intron (50 splice site) and transfer to 20 OH of an adenosine near the end of the intron (branch point). The second chemical step results in cleavage of the bond at the end of the intron (30 splice site) and transfer to the 30 OH created in the first reaction, which joins the flanking exons. 
These reactions are catalyzed by the spliceosome, a complicated assembly of five small nuclear RNAs (snRNAs) and dozens of proteins.In many organisms, the output of splicing is often further elaborated through alternative splicing, which tweaks the protein coding capacity and the stability of the resulting mRNAs by the selective inclusion or skipping of exons, retention of introns, and choice of alternate 50 or 30 splice sites. Alternative splicing adds an important layer to gene regulation that is exploited in many biological pathways including developmental programs, neuron identity, and metabolic potential, to name just a few.  Small molecules that target individual spliceosome components provide a flexible way to probe their function and uncover new details of spliceosome assembly. Researcher also consider the potential for inhibitors to study the numerous cellular pathways that are impacted by splicing, and as drug leads for diseases in which splicing regulation plays a critical role.


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