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Meta Description: Recent discoveries regarding the molecular regulatory mechanisms governing RNA processing, alternative splicing, and pleiotropic functional profiles of splicing proteins may provide the foundation for therapeutic innovation against difficult to treat diseases associated with aberrant RNA processing or inappropriately amplified expression of specific gene products.
The nuclear synthesis of mature messenger RNA (mRNA) from precursor mRNA (pre-mRNA), the primary transcript generated from the genomic DNA, is initiated by the recruitment of specific spicing regulators via adaptor complexes and assembly of a prespliceosome on the target nascent pre-mRNA. It requires a coordinated cotranscriptional and posttranscriptional pre-mRNA processing and splicing for noncoding intron removal along with a concerted action of several transcription factors and RNA polymerase II elongation complex.
Canonical splicing of pre-mRNAs usually involves 2 transesterification reactions mediated by a catalytically active spliceosome, the major element of the splicing machinery, that undergoes a dynamic multistep assembly, rearrangement and catalytic site remodeling for its activation. Spliceosome as an evolutionarily conserved unique mixed protein/RNA enzyme is a macromolecular ribonucleoprotein (RNP) complex that displays a dramatic structural and compositional dynamics with massive remodeling of its RNP subunits.
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