General Genetics/Splicing

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Introns are intervening RNA sequences that do not code for proteins or serve other functions. They lie between coding regions of RNA known as exons. During eukaryotic mRNA processing, the introns are excised and exons are spliced together to form the mature mRNA transcript. One pre-mRNA can give rise to different mature mRNA transcripts through alternative or differential splicing, wherein the exons are spliced in different permutations.

How Self-Splicing led to the RNA World Hypothesis[edit]

In the protozoan Tetrahymena, a rare form of "self-splicing" takes place wherein no proteins are required. The RNA folds into a secondary structure which excises introns. This was discovered by Tom Cech, who won the Nobel Prize in 1989 for his discovery of catalytic RNA.

The discovery of catalytic RNA led to the RNA World Hypothesis, which postulated that earlier forms of life may have relied solely on RNA to store genetic information and catalyze chemical reactions. However, many scientists believe that RNA is too unstable (due to its highly reactive 2'-OH group) to reliably give rise to life.

The Lariat Model of Intron/Exon Splicing[edit]

Small nuclear ribonucleoproteins (snRNPs) are formed from a combination of small nuclear RNA (snRNA) and helper proteins. These join with other proteins to form a spliceosome assembly.

Pre-mRNA has guanine (G) nucleotides at the 5' side of its introns. Towards the middle of the intron is an adenine (A) nucleotide. The spliceosome will fold the intron such that the G and A are next to each other. The oxygen of the A's 2' hydroxyl group attacks the 5' phosphate of the G. The G detaches from the 3' end of the exon to form a loop with the A. The hydroxyl group at the 3' end of the newly-formed exon attacks the phosphate group at the beginning of the next exon. The intron lariat is completely excised from the mRNA.