Structural Biochemistry/Nucleic Acid/RNA/RNA modification/RNA Splicing

RNA splicing takes place after RNA is transcribed from DNA, but before RNA is translated into mRNA. Splicing takes out the interfering sequences (introns) from the expressed gene sequence (exons). Small nuclear RNAs (snRNAs) contain less than 300 nucleotides and are located within the nucleus. They are mainly used for splicing mRNA precursors and are labeled as U1, U2, U3, U4, U5, and U6.

Small Nuclear RiboNucleoprotein Particles (snRNPs) are the secondary molecules made of small nuclear RNAs (snRNAs) and specific proteins. snRNP molecules make up the larger splicosome molecules. U1 snRNP recognizes the binding site on the 5’ end and the six-nucleotide sequence of the U1 snRNA binds to the splice site on the pre-mRNA. From this, the spliceosome will assemble along the pre-mRNA molecule. The U2 snRNP will bind to the branch site on the intron with its complementary sequence between the U2 snRNA sequence and the pre-mRNA. The U4, U5, and U6 snRNPS then bind with the U1 and U2 complexes and form the necessary spliceosome. The splicing process itself begins with the U5 interaction with the exon sequence on the 5’ splice site. The U6 goes through intramoleculear reorganization after breaking from U4, which allows U2 to base pair and interact with the 5’ end of the intron, taking U1 out of the spliceosome. The U2-U6 complex forms a helix that forms the center of the spliceosome itself. U4 prevents U6 from splicing until the splice sites are correctly aligned. Once alignment has occurred, the transesterification reaction cuts the 5’ exon at the phosphodiester bond and produces a lariat intermediate. Splicing continues with rearrangements with the spliceosome that will then produce the next transesterification reaction on the pre-mRNA. In the rearrangement, the U5 aligns with the 5’ exon so that it is easier to attack the 3’ splice site to produce another spliced product. To finish the splicing process, the U2, U5, and U6 release itself from the lariat intron.