RNA Splicing: Regulation and Dysregulation in the Heart

RNA Splicing: Regulation and Dysregulation in the Heart

Maarten M.G. van den Hoogenhof, Yigal M. Pinto, Esther E. Creemers

Two-step splicing reaction. Splicing occurs by a 2-step trans-esterification reaction to remove introns and to join exons together. In the first step, U1 small nuclear ribonucleoprotein (snRNP) assembles at the 5′ splice site of an exon and U2 snRNP at the branch point sequence (BPS), just upstream of the 3′splice site of the adjacent/downstream exon. This configuration is known as the prespliceosome. Hereafter, U1 and U2 are joined by the snRNPs U5 and U4–U6 complexes to form the precatalytic spliceosome. Next, U4–U6 complexes unwind, releasing U4 and U1 from the prespliceosomal complex. This allows U6 to base pair with the 5′ splice site and the BPS. The 5′ splice site gets cleaved, which leads to a free 3′ OH-group at the upstream exon, and a branched intronic region at the downstream exon, called the intron lariat. During the second step, U5 pairs with sequences in both the 5′ and 3′ splice site, positioning the 2 ends together. The 3′ OH-group of the upstream (5′) exon fuses with the 3′ intron–exon junction, thereby conjoining the 2 exons and excising the intron in the form of a lasso-shaped intron lariat. Finally, the spliceosome disassembles, and all components are recycled for future splicing reactions. [Powerpoint File]

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