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.
Back to thinking about how to explain alternative splicing in an easy, graphical or pictorial way.
Here’s an attempt at sketching plant cells under a microscope. Grid like arrangement of cells, with chloroplasts (photosynthesis organelles) as greenish circles, and the cell nucleus as dark circles/blobs.
Not entirely sure where this is going…maybe a cartoon. Still hope to include Pandas somewhere along the line…
Starting on making GATEWAY gene constructs for making RNA binding protein-GFP fusions for iCLIP and RIP, along the lines of work by the Staiger group (with nice link to ‘Living in an RNA World‘ blog post). Been trying out SnapGene to manipulate and visualise DNA sequences….so far so good (way better than Vector NTI).
The RNA Journal is twenty years old and as part of their anniversary around 130 researchers in the field of RNA biology have contributed some of their personal reflections of working in this area. Contributors include Douglas Black, Michael Rosbash and Alberto Kornblihtt.
I’ve browsed through some of the essays and one that caught my attention was ‘Thoughts on NGS, alternative splicing and what we still need to know‘ by Kristen Lynch. Here she emphasises the need to determine the functional consequences of alternative splicing for an organism, and as she pointedly says ‘To truly appreciate the full impact of alternative splicing on biologic processes, and argue against those who wonder if it might all be “noise,” we need to do better. The question is how to achieve this goal’. [Note that NGS in the title of the article refers to Next Generation Sequencing]
As a relative newcomer to the field of AS, I think it’ll be useful for me to delve into these articles – they seem to be a refreshing way to learn how quickly research into AS has ‘evolved’ as well as providing an honest outlook as to what areas seem to be a priority for future work.
The cover art in interesting too – it is entitled ‘Group in Sea, 1979, by Philip Guston‘. He was an American abstract expressionist painter.
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I’ve been working with Ally Wallace to develop cartoon-like drawings that illustrate our research – here is some work in progress. I like the lab soundscape in the background. The aim was to develop something that might appeal to a younger audience, and tries to take an imaginative approach to the subject. Maybe a bit too wordy, so I’m now doing much more stripped back drawings – these were all done on an iPad using the ProCreate app. Then again, maybe it would be better as a short pamphlet/book….let’s see.
I was asked the other day if I could explain our research in 45 seconds, and after fumbling about with cumbersome nuggets such as ‘post-transcriptional mechanism’ and ‘spliceosome‘ and ‘exon-intron junctions’ decided it probably needed a drastic change of tact!
Anyway, it struck me that one of the key things to get across about alternative splicing is how important the inclusion (or exclusion) of an exon in a pre-mRNA has on how the mRNA is read or interpreted. If you substitute reading RNA messages with English grammar it reminds me of a funny Panda-related sentence that Hugh introduced me to a while back. It emphasises just how important a comma (or alternate exon, for example) has on the whole interpretation of the message. Compare these two sentences describing Pandas:
Eats shoots and leaves OR Eats, shoots and leaves
Notice how the comma completely changes the whole meaning and interpretation of the statement.
I think that this could be a good way to try to put across the key feature of splicing. Can it be done in 45 secs? Watch this space!
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