abundance of transcript=amount of protein?

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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.

Splicing based body-temperature thermometer

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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.

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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.