Courtesy of @lopsidedlablife, here is another alternative splicing visual. This follows on from ‘Let’s eat grandma‘, and is based on the idea of how punctuation can greatly influence the meaning of a statement, akin to how the inclusion/exclusion of alternative exons during pre-messenger RNA splicing can massively influence the ‘meaning” of the spliced message e.g. the introduction of new coding sequence that might adapt protein function by adding an extra functional domain(s), for example, or might influence the levels of functional or ‘translatable’ message if a premature termination codon is included in the alternative exon. The review ‘Alternative splicing in plants – coming of age‘ by Syed et al. 2012 gives a great overview of pre-messenger RNA splicing in plants.
The visual is of course greatly influenced by the famous Banksy graffiti….however there is some speculation as to whether it was actually a true Banksy. Here the Panda is proudly shooting ‘Splice’ & ‘Sites’ from a couple of clown guns.
See how a single comma can totally change the meaning of what Pandas do best (they ‘Eat shoots and leaves’), turning the cute Panda into a (clown) gun-toting splicing bear, that ‘leaves’ the scene of the splicing crime (‘Eats, shoots and leaves)…
..or put another way:
See Panda alternative splicing, see pandAS…
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Thinking about how to encapsulate alternative splicing in one ‘killer’ picture.
The picture above is what I came up with….
The analogy is that the inclusion/exclusion of alternative exons during pre-mRNA splicing can have the same dramatic effects as the inclusion/exclusion of key punctuation in a sentence.
I sincerely apologise to all Grandmas seeing/reading this….
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Thought that this was an interesting paper, published recently in PNAS.
The paper shows that alternative splicing produces different transcript isoforms for the 5’UTR region of the human gene encoding α-1-antitrypsin called SERPINA1, such that splicing of 5’UTR modulates the inclusion of long upstream ORFs (uORFs). What’s new with all this I hear you say. Well, the authors go on to show that while SERPINA1 transcripts produce the same protein isoform, they do so with different translation efficiencies. Differences in uORF content and 5’UTR secondary structure combine to differentiate the translational efficiencies of SERPINA1 transcripts.
α-1-antitrypsin is of interest because deficiencies in this protein are associated with chronic obstructive pulmonary disease (COPD), liver disease, and asthma. This work points to the possibility that genetic alterations in noncoding gene regions, such as the 5’UTR region, could result in α-1-antitrypsin deficiency.
The work also reinforces the idea that the amount of protein produced from a gene is not a simple function of the abundance of the transcript.
The reference is: Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):E10244-E10253. doi: 10.1073/pnas.1706539114. Epub 2017 Nov 6.
The image used is their Figure 3. SHAPE-MaP structure probing data for SERPINA1 transcripts.
This work from the Lab of RNA Biochemistry at the Freie University Berlin shows just how sensitive splicing is to small changes in body temperature.
They looked at alternative splicing (AS) of U2af26 across a physiologically relevant temperature range (35-40oC). [U2af26 is a component of the essential splicing factor U2af (U2 auxiliary factor) where it can substitute for U2af35 in heterodimers with U2af65]
The authors show that U2af26 exon 6/7 skipping showed a very nice linear correlation with the temperature (see their figure below), suggesting that AS is able to react in a thermometer like way to read body temperature changes.
The paper goes on to show an involvement for SR proteins in temperature-regulated U2af26 AS, primarily via modulation of the phosphorylation state of SRs. The authors speculate that there will be a physiological role for temperature-controlled AS in other phenomena, such as hypothermia and fever.