I'm seriously beyond impressed with this new study at BiorXiV. What an amazing amount of work in a critically under-developed area!
I feel like this stuff comes up all the time. How do we study what is happening between the RNA and protein. If you're thinking -- bleh -- who cares -- didn't Rosalind Franklin and some guys who lucked out because some crazy alcoholic congressman hated Linus Pauling solve all the DNA--> RNA --> protein interaction stuff? We have the central dogma, right? We're good to go!
Easy to think that but -- it turns out that it's way way way more complex than this. You know how they teach us there is like 4 nucleotides?
.... As of 2006 there were over 100 post-transcriptional modifications of RNA nucleotides known and I know 2 people that are working on studying new ones and whether they are biologically relevant. I only learned this recently and I was inconsolably depressed about it for like 4 minutes. For real. That's messed up.
Okay -- so with that in mind. Let's go into a less comfortable framework. Maybe we don't know ANYTHING about how protein and RNA interact, why they do it, and what happens when they don't do it right? What the Heck do you do when someone asks you to study these things? If it's an email, you could probably pretend it went to your junk filter for -- what? -- 5 weeks? That's fair, I think. If you've got an office, though, you're probably going to get an appointment request by week 6.
What do you do? Schedule and appointment for 2pm and take a Xanax at lunch? (Obviously -- your legally obtained, doctor prescribed medication -- I assume having an office automatically qualifies you for some sort of anti-anxiety medication. Everyone knows where to find you now!)
This paper is huge and kind of intimidating. It's in BioRxiV now, but this should be in Cell or something equally impressive soon, I'm sure. But check this out. You can go to https://www.xrnax.com/theprotocol and the website walks you through something huge and scary like RNA/Protein interactions -- unbiased -- ridiculously powerful -- and it starts like this --
It's got photographs of everything. All the steps. All the materials and methods are so clearly described and pictured that I could probably do it.
I bet that's the clear stuff!!
It doesn't stop at the sample prep. The different levels of experimental design depending on what your question is. Do you want to know exactly where the nucleotides and proteins interact. Do you need something focused or quantitative global (SILAC)? its' all in here.
Applications of this XRNAX are described in the paper and at XRNAX.com, but I suspect this is just the very tip of a huge iceberg. There is so much that we can do with this. There are a ton of fundamental biological questions to go after -- you can't tell me that when cells are irradiated or blasted with free radicals that it just busts up DNA -- other things have to be affected -- but DNA is the only thing we've ever really looked at (cause it's way easier). XRNAX gives us a whole lot of ways to look these complex interactions that I don't think we've had before.
While I'm just rambling. There are lots of other gems in this study. This is the first time I've seen the awesome MSFragger in action (indiscriminate PTM IDs -- they do +1000Da!!). I should probably stop typing about this, but -- wow -- you should really check this out!