Question

What role does the UACUAAAC sequence play in the lariat model of splicing?

Answer 1

Hey there,

You posed a very interesting question! I'll do my best to supply you with a decent answer.

So as you know, the lariat is the structure formed by the intron as it is excised from the mRNA transcript. This splicing of the RNA is accomplished through the spliceosome - a complex of small nuclear RNAs (which do most of the work) and protein subunits.

There are three important nucleotide sequences in the intron that allow the spliceosome to recognize it. The first is the 5 prime splice site, the second is the 3 prime splice site, and the third is the branch point.

Here's what it would look like:
5' end.......Exon 1.......5' Splice Site.....Branch Point......3' Splice Site.....Exon 2.....3' end
The intron is located between the 5' and 3' splice sites.

In Saccharomyces cerevisiae, the branch point sequence is: UACUAA*C. I starred that Adenine for a reason - that's the one that binds to the 5' splice site to form the lariat. Normally, phosphodiester bonds link the nucleotides from the 5' carbon to the 3' carbon. That specific adenine binds two nucleotides to form the loop: one at its 3' carbon, but another at its 2' carbon.

I'll add in a diagram later to better show you.

Since the site is shutting down very very soon, I'll have to rush a bit and skip over the details, but I hope htis helps!

Answer 2

thank you for what you have responded so far :)

Answer 3

Hey! Apologies for the late reply. Here is the diagram I promised.

This is a pretty cool looking picture that I stole and labelled. Okay - so you have the 5' end of the mRNA top right, and the 3' end floating down at the bottom there.

In white you have the specific S. cerevisiae "Branch Point" sequence you mentioned earlier. In orange is the important adenine I started to talk about before. And in blue, you have an RNA / protein complex called U2 (like the band!).

So what's going on here? The red adenine is connected to its adjacent white Adenine through a regular 5'-->3' connection. But, as you can hopefully see, it's also binding to the free end of the intron. That adenine has two phosphodiester bonds - stabilizing the structure of the lariat.

Okay - so hopefully that's clearer now, but what about the sequence itself? Why's it so important?

It turns out that you have this RNA/protein molecule, U2, which specifically recognizes and pairs complementary to the intron. A from U2 binds with U from intron, U from U2 binds with A from intron, etc. etc...but wait! You'll notice that there is NO complementary base for the red adenine. What this does is to "push" the adenine out - making it available to bond to the free end of the lariat! In essence, the reaction is catalyzed through this ingenious trick of natural selection. Cool, right?

After the lariat is formed, you'll see that the exons are connected together (green arrows). This reaction, like the other ones, is mediated by the small nuclear Riboproteins (complexes of RNA and protein subunits).

Answer 4

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