Imagine pre-messenger RNA as ….

Irn bru research

Ok, lets talk about pre-messenger RNA splicing, shall we?

Mmmm, na it’s a bit complicated. Hang on, it might be easier to use Scotland’s ‘other national drink’, the very orange ‘Irn Bru‘ to think about what’s going on here.

RNA pre-messages usually have strings of sequence made up of A’s, C’s, G’s and U’s. But let’s imagine that a pre-mRNA is the ode to Irn-Bru (see picture above), and that chunks of the message are removed – or spliced out – to leave a final useable message. See how the meaning of the original pre-message bears no resemblance to the final message? (and the ways messages are spliced can result in very different outcomes).

Irn Bru is the same colour as ethidium bromide DNA gel stain (…or SyBr safe, if you’re younger)]. Might test Irn-Bru for its DNA staining ability (it has mystical properties after all), but I’ll leave someone else to test whether EtBr/SyBr safe passes for Irn Bru*

* disclaimer no responsibility is hereby taken if anyone actually does this…

(Editor: did you know that Scotland is one of the few places in the Western world where Coke is not the no.1 top selling soft drink. In Scotland Irn Bru is the top selling soft drink.)

Follow us on Twitter @SpliceTime

Let’s eat grandma

lets eat grandma cropped

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….

Follow us on Twitter @SpliceTime


abundance of transcript=amount of protein?

Screen Shot 2018-03-17 at 09.31.21

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.

Splicing based body-temperature thermometer

Screen Shot 2018-03-06 at 07.06.39

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.

Screen Shot 2018-03-06 at 07.06.01

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.