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Beschreibung

Most eukaryotic genes are expressed as pre-mRNAs that are converted to mRNA by splicing. In this process noncoding sequences (introns) are removed, and coding sequences (exons) are ligated together. Some exons are known to be constitutively spliced and are present in every mRNA produced from a given pre-mRNA. However, many are alternatively spliced to generate variable forms of mRNA from a single pre-mRNA species. Nuclear pre-mRNA splicing is catalyzed by the spliceosome that is a multi-megadalton ribonucleoprotein (RNP) complex. It removes introns from nuclear pre-mRNA. The conformation and composition of spliceosome is shown to be dynamic, which is critical for its high degree of accuracy and flexibility. In most eukaryotes two unique spliceosomes have been described: the U2 -dependent spliceosome that catalyzes the removal of U2-type of introns and the U12-dependent spliceosome that is present only in a subset of eukaryotes and splices U12-type of intron. Introns are removed by two consecutive transesterification reactions. In the first reaction the 2 OH group of the branch adenosine of the intron carries out a nucleophilic attack on the 5 ss, which results in cleavage at this site and ligation of the 5 end of the intron to the branch adenosine, forming a lariat structure. In the second reaction, the 3 ss is attacked by the 3 OH group of the 5 exon, which leads to the ligation of the 5 and 3 exons forming the mRNA, and release of the intron. (Ref.: Matera, AG., and Wang, Z. (2014). Nat. Rev. Mol. Cell Biol. 15(2), 108-121, Will, CL., and Luhrmann, R. (2011). Cold Spring Harb. Perspect. Biol. 3(7), a003707, Patel, AA., and Steitz, JA. (2003). Nat. Rev. Mol. Cell Biol. 4(12), 960-970).