Monday, June 12, 2017

Chimeric fusion RNAs in noncancerous cells!

Biology is really complicated. Just throwing that out there.  It would be really great it if it would just all obey the central dogma...

 ....and we could get back to running our perfectly calibrated and QC'ed instruments (thanks, WikiPedia article on Chimeric RNA!), but then it throws us completely new (at least to me) concepts like Chimeric Fusion RNAs, which are the topic of this cool paper!

I'm familiar with how screwy DNA/RNA can get in cancer and how complex these mixups can be at every level (transflips, for example?)...but...come on....RNA can't be just binding to other RNA and making messed up protein in normal human tissue, right?!?!?

This team shows some convincing evidence that it is and does. They started by looking at RNA-Seq from nearly 300 different libraries and found loads of reads coming back that could only mean that this gene over here and this gene over here were somehow fused in making weird RNA, but they only found them in these tissues...

...yeah, like all of them.

If you've ever looked at RNA-Seq data, or sat through a talk on it where someone understands it and is being honest about the technique you know that there is a lot of noise in the data. Part of the reason their informatics and statistics are so advanced is that they have to be in order to get to the good stuff. So maybe this is all just noise and false positives?

That figure at the top of the paper? This is a clip from this study where they use PCR to amplify some of these products and visualize them on gels (not much noise there), the very top is Sanger Sequencing of RT-PCR products and the bottom is MS/MS that shows that some of these weird fusions are making it to expressed proteins.

In "normal" tissue! Maybe this is what a lot of our unidentified spectra are...?....if so, the only way to get to them is going to be more informed FASTA databases that include these tissue or individual specific fusions as options for database search....or de novo peptide sequencing that can BLAST back to short chains from multiple gene products...

Either way, biology is complicated...and it would be a whole lot less fun if it wasn't!

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