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Splicing - Nature
Splicing - Nature
What's the difference between mRNA and pre-mRNA? It's all about splicing of introns. See
how one RNA sequence can exist in nearly 40,000 different forms.
For most eukaryotic genes (and some prokaryotic ones), the initial RNA that is transcribed from a gene's
DNA template must be processed before it becomes a mature messenger RNA (mRNA) that can direct the
synthesis of protein. One of the steps in this processing, called RNA splicing, involves the removal or
"splicing out" of certain sequences referred to as intervening sequences, or introns. The final mRNA thus
consists of the remaining sequences, called exons, which are connected to one another through the
splicing process. RNA splicing was initially discovered in the 1970s, overturning years of thought in the
field of gene expression.
alternative splicing.
Alternative splicing refers to the process by
which a given gene is spliced into more than
one type of mRNA molecule.
Copyright National Institutes of Health
Early in the course of splicing research, yet another surprising discovery was made; specifically,
researchers noticed that not only was pre-mRNA punctuated by introns that needed to be excised, but also
that alternative patterns of splicing within a single pre-mRNA molecule could yield different functional
mRNAs (Figure 2; Berget et al. 1977). The first example of alternative splicing was defined in the
adenovirus in 1977 and demonstrated that one pre-mRNA molecule could be spliced at different junctions
to result in a variety of mature mRNA molecules, each containing different combinations of exons.
Shortly afterward, alternative splicing was found to occur in cellular genes as well, with the first example
identified in the IgM gene, a member of the immunoglobulin superfamily (Early et al., 1980). Another
example of a gene with an impressive number of alternative splicing patterns is the Dscam gene from
Drosophila, which is involved in guiding embryonic nerves to their targets during formation of the fly's
nervous system. Examination of the Dscam sequence reveals such a large number of introns that
differential splicing could, in theory, create a staggering 38,000 different mRNAs. This ability to create so
many mRNAs may provide the diversity necessary for forming a complex structure such as the nervous
system (Schmucker et al., 2000). In fact, the existence of multiple mRNA transcripts within single genes
may account for the complexity of some organisms, such as humans, that have relatively few genes
(approximately 20,000). For example, work from Wang et al. (2008) suggests that more than 90% of human
genes are alternatively spliced.
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Chow, L. T., et al. An amazing sequence arrangement at the 5 ends of adenovirus 2 messenger RNA. Cell 12, 18 (1977)
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Early, P., et al. Two mRNAs can be produced from a single immunoglobulin chain by alternative RNA processing pathways. Cell 20, 313319 (1980)
Knapp, G., et al. Transcription and processing of intervening sequences in yeast tRNA genes. Cell 14, 221236 (1978)
Konarska, M. M., et al. Characterization of the branch site in lariat RNAs produced by splicing of mRNA precursors. Nature 313, 552557 (1984) doi:
10.1038/313552a0 (link
to article)
Patel, A. A., & Steitz, J. A. Splicing double: Insights from the second spliceosome. Nature 4, 960970 (2003) doi:10.1038/nrm1259 (link
to
article)
Pierce, B. A. Genetics: A Conceptual Approach, 2nd ed. (New York, Freeman, 2000)
Roy, S. W., & Gilbert, W. The evolution of spliceosomal introns: Patterns, puzzles, and progress. Nature Reviews Genetics 7, 211221 (2006) doi:
10.1038/nrg1807 (link
to article)
Schmucker, D., et al. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell 101, 671684 (2000)