The regulation of Pre-Messenger RNA splicing

Published on October 1, 2007 Archived on July 30, 2015   31 min

Other Talks in the Therapeutic Area: Oncology

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The regulation of pre-messenger RNA splicing. The regulation of eukaryotic gene expression is controlled in diverse ways. In addition to the primary mechanisms that turn the transcription of a gene on and off, there are many post-transcriptional steps downstream in the gene expression pathway, where the protein output of a gene can be modulated. In this talk, I'll describe the regulation of the pre-mRNA splicing reaction, and how this reaction can be adjusted to produce multiple mRNAs and hence, protein products from the same gene. This type of regulation is often called alternative splicing. In prokaryotic cells, the primary RNA transcript
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of a gene can be directly translated into protein. However, in eukaryotes, things are much more complex. In eukaryotic cells, mRNAs are transcribed as long precursor molecules that must undergo several RNA processing reactions prior to exportation from the nucleus and translation in the cytoplasm. The first processing reaction is the addition of
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a special methylated guanosine nucleotide to the five-prime end of the RNA transcript. This cap nucleotide is connected via special five-prime to five-prime phosphotriester linkage directly to the first nucleotide of the RNA transcript. At the other end of the gene, a two-step processing reaction takes place called cleavage and polyadenylation. This involves, first, removal of the three-prime end of the RNA by an endonucleolytic cleavage at a special sequence, the poly(A) site. After removal of the 3-prime piece, a special enzyme, the poly(A) polymerase, adds between 100 and 250 adenosine residues to the new three-prime end, creating a three-prime poly(A) tail on the RNA. Both capping and polyadenylation are coupled to the transcription of the RNA polymerase II and are important for the subsequent processing, transport, and translation of the mRNA, and the maintenance of its stability. The third RNA processing reaction is pre-mRNA splicing, which involves the clipping out of internal or, intervening sequences from the RNA and the joining, or ligation, of the remaining segments together. The segments that are removed from the RNA are called introns, and the segments in the sequence that remain in the final mRNA transcript are called exons. Both cleavage, polyadenylation, and splicing are regulated by similar mechanisms but, in this talk, we will only discuss splicing. The most complex RNA processing reaction in the cell is pre-mRNA splicing.
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The regulation of Pre-Messenger RNA splicing

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