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A quick look at mRNA Splice Variants

04 Apr
-Beadle and Tatum Redux

-Beadle and Tatum Redux

In my microbiology class this past week, we were discussing how prokaryotes and eukaryotes differ in their handling of DNA, RNA and gene regulation. Mostly, we focused on how the presence of the nuclear membrane in eukaryotes separates the processes of transcription and translation and what this results in. Briefly, bacteria are prokaryotic life forms that lack a defined nucleus (among other differences). Because of this, when bacteria transcribe mRNA, it is immediately available for translation – the DNA, RNA polymerase and Ribosome all exist in shared space. Below is a classic image of a strand of DNA(stretching left to right) in E. coli being transcribed into RNA. The RNA molecules extend away from the DNA and appear to travel up or down away from the DNA in this micrograph. Along the length of the RNA, we see dense ribosomes which are busy synthesizing proteins.

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In Eukaryotes, the nucleus encases the DNA, the RNA polymerases and mRNA. mRNA can be completely synthesized and modified in a number of ways before they are exported from the nucleus to the cytoplasm, where ribosomes will translate the message into protein.

One of the modifications of Eukaryotic mRNA we spoke about was splicing. Splicing is a means of snipping segments of non-coding introns out of the mRNA leaving a mature mRNA with a continuous strand of exons. One interesting possibility this enables is the production of alternative sequences made from differential splicing of the immature mRNA. These alternative mRNAs are known as splice variants. At this point, I was asked for an example of a gene that is handled in this way and was caught flat-footed.

Hmm. Perhaps this is something that I’d heard so much about in classes but never in the ‘real world’. I’ll have to look.

One of the first things I found was this discussion of splice variants suggesting that this was not a biologically significant event. i.e., the RNA may be alternatively spliced, but do these splice variants actually result in functional proteins with different properties. The author poses a challenge to find examples of splice variants that are ‘real’. The ensuing discussion is a good one.

What would this looks like?

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Regardless, I found a paper with some good figures that may help students understand how this phenomenon (at least putatively) occurs.  Here’s the best figure presenting a diagram of the different mRNAs created and gels and sequence data indicating that these exist.

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The above Figure shows the presence of distinct RNA species, although that, alone, does not mean that these RNA are ever made into protein. To do that, western blots of protein extracted from various tissues is shown below.

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What is left to find is whether each of these two proteins actually does something. Are both forms required? Are their functions distinguishable?
My quick look through the literature did not uncover any evidence for this last question. If anyone out there knows the literature on this, I would love a push in the right direction. It doesn’t matter what gene we’re looking at, just that it is an example of alternative splicing and that each of the splice variants is actually made and has some identifiable and distinct function.
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1 Comment

Posted by on April 4, 2014 in Uncategorized

 

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One response to “A quick look at mRNA Splice Variants

  1. ratabago

    April 13, 2014 at 10:01 am

    These might help, I found them interesting, anyway.

    Identification of a Functionally Distinct Truncated BDNF mRNA Splice Variant and Protein in Trachemys scripta elegans: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0067141

    A Novel Actin mRNA Splice Variant Regulates ACTG1 Expression: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003743

     

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