Principles of Biochemistry Volume 3 - A. Lehninger 1985

Molecular mechanisms of genetic information transfer
DNA replication and transcription
Introns must be removed from mRNA precursors

In The eukaryotic Nucleus, mRNAs must undergo further Processing stages, which involve the removal of introns (Section 27.28). The Nucleus contains a special Class of RNA that undergoes very rapid turnover during Protein Synthesis. This RNA is known as heterogeneous nuclear RNA (hnRNA) and consists of a mixture of very long RNA molecules. Although it had long been suspected that hnRNA molecules serve as precursors to cytoplasmic messenger RNAs, researchers were nonetheless puzzled by the discrepancy between the structures of hnRNA and mature cytoplasmic mRNAs. Specifically, hnRNA is much larger in size than mRNA, and the former also exhibits a greater diversity of nucleotide sequences than the latter. For quite some time, this problem seemed enigmatic, but its solution became apparent following the discovery of untranslated intervening sequences, or introns, in eukaryotic genes. Recall that introns are frequently much longer than exons, i.e., the coding portions of the Gene (Section 27.28). Following the discovery of introns in DNA, a natural question arose: are they transcribed collinearly along with exons to form a very long mRNA precursor that is complementary and collinear to both exons and introns, or does RNA polymerase “skip” over the introns and transcribe only the exons?

This question has now been resolved. It turned out that eukaryotic RNA polymerase transcribes both exons and introns in the exact sequence in which they occur within the gene. This process generates very long RNA precursors containing untranslated RNA segments that are complementary to The nucleotide sequences of DNA introns. Such mRNA precursors constitute a significant portion of hnRNA and are found exclusively in the nucleus. Furthermore, the structural relationships between hnRNA and their corresponding cytoplasmic mRNAs are explained precisely by the presence of introns. However, as soon as one mystery was solved, another immediately took its place.

It was necessary to determine how the nuclear mRNA precursor, containing blocks of introns, is converted into mature cytoplasmic mRNA, from which these blocks must be absent. If the mRNA precursor were simply cleaved at every point where an exon ends and an intron begins, or conversely, where an intron ends and an exon begins, this would result in the generation of A large number of mRNA precursor fragments in the nucleus, some of which encode polypeptide chain segments while others are untranslated. How can these separated coding fragments be assembled in the correct order and joined together to form mature mRNA?