Module 7: Molecular Computing with RNA Sequences

 

Intron/Exon Boundary Sequences, Splice Variants

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  • RNA splicing mechanisms: In eukaryotes, protein-coding RNA is transcribed as a molecule (nuclear mRNA) which is converted into mRNA by the splicing out of internal sequences called "introns". The coding sequence in the mRNA is derived from internal sequences called "exons" which alternate with the introns in the longer, nuclear mRNA. (Figure of splicing mechanisms)

    Splicing of nuclear mRNA is catalyzed by specialized RNA-protein complexes called small nuclear ribonucleoprotein particles (snRNPs). The RNAs found in snRNPs are identified as U1, U2, U4, U5 and U6 (snRNAs). The genes encoding these snRNAs are highly conserved in vertebrate and insects and are also found in yeasts and slime molds indicating their importance. The uRNA Database provides aligned, annotated and phylogenetically ordered uRNA sequences.

  • RNA Enzymes: RNA can engage in intramolecular catalysis including self-splicing and in some cases can act as an enzyme. A wide variety of rRNA molecules and some mRNA molecules (chloroplast and mitochondrial) can splice themselves. These molecules are called ribozymes (RNA enzymes; Figure of a Ribozyme) and some of these molecules show other enzymatic functions (RNA Editing Web Site)

  • Search for consensus intron/exon sequences: Analysis of a large number of mRNA genes has led to the identification of highly conserved consensus sequences at the 5' and 3' ends of essentially all mRNA introns.(Figure of Consensus Splice Sites) A majority of these searches are based on algorithms that look for complete genes. The Gene Finder site from the Baylor College of Medicine has a variety of options to search for introns and exons such as predictions of 5', 3' and internal exons, donor and acceptor splice sites, and multiple splice variants. A gene prediction method based on the Hidden Markov Model of probabilities (HMMgene) also can locate donor and acceptor sites.

  • Splice variants: Alternative splicing, resulting in different combination of exons, has been found to occur in the primary transcripts of at least 40 different genes. By altering the pattern of exons that are spliced together different proteins can arise from the primary transcript coded in a single gene. Alternative splicing can occur either at specific developmental stages or in different cell types. The Gene Finder and HMMgene are two sites that can search for alternatively spliced variants of a gene.


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