Prp8

IntroductionIntroduction

Pre-mRNA SplicingPre-mRNA Splicing

Splicing is an essential process in the cell is because immediately following transcription, the pre-mRNA contains both intronic and exonic sequences. The exonic sequences are the protein coding portions of the RNA which contain codons that directly specify which amino acids will be incorporated into a newly synthesized protein. Conversely, the intronic sequences are non-coding portions of the pre-mRNA which need to be removed in order to form an uninterrupted coding sequence known as mature-mRNA. If the non-coding intronic segments were not removed from pre-mRNA, the cell would be unable to synthesize the protein coded for by the mRNA, subsequently inhibiting the synthesis of new proteins.

Pre-mRNA splicing is carried out by one of the most complex pieces of cellular machinery known to date; the Spliceosome. It is a large, catalytic protein-RNA complex responsible for removing the intronic sequences of pre-mRNA and “splicing” together the exonic sequences to form mature mRNA. The spliceosome is made up of approximately 145 distinct spliceosomal proteins, and five small nuclear RNAs (snRNAs) . The five snRNAs have been subsequently named U1, U2, U4, U5, and U6. The spliceosome carries out a two-step transesterification reaction through a series of chemical steps in order to remove the intronic sequences from the pre-mRNA, which is facilitated by the movements, rearrangements, and dynamic exchanges of the snRNAs and splicing associated proteins . First, the U1 snRNP recognizes and binds to the 5’ splice site of the pre-mRNA and the U2 snRNP recognizes and binds to the branch site of the intronic sequence, which contains a conserved adenine nucleotide, which is collectively known as complex A . Subsequently, the U4/U6 U5 tri-snRNP moves in and associates with the intronic sequence (now known as complex B). This causes the U4 and U1 snRNPs to be displaced, forming the catalytically active spliceosome (complex B*) and the remaining U2, U5, and U6 snRNP facilitate the two transesterification reactions, dissociate from the now mature mRNA, and are recycled for subsequent use in another splicing reaction .