Thursday, March 10, 2011

Weekly RNA News - Week X - March 2011

Scott, Coyle, and Doudna @ Berkeley
Xrn1: Structure of a messenger RNA degrading enzyme in complex with three DNA thymines.
Molecular Cell, 41, 600-608 (2011)

The Doudna lab comes again with another interesting structure related to RNA mechanics. As Scott, Coyle, and Doudna say in their paper, there is only one enzyme with the task of degrading mRNA in the cytoplasm of eukaryotic cells, this enzyme is called Xrn1, which sounds a lot like a sci-fi movie to me. They also say that the enzyme weighs 175 kDa, and is conserved from yeast to mammals. In order to crystallize the structure they used DNA instead of RNA. This you can see in the structure with PDB_ID:2Y35. The idea of the trick is that it takes longer for Xrn1 to degrade DNA than RNA, and the mechanism of degradation is assumed to be similar enough to that of an mRNA since it is based mainly on recognition of an RNA substrate "marked" by a 5'-monophosphate.

In the following image you can clearly see how Histidine 41 and Triptophane 540 kind of make a stacking trap of the three thymines, you can also see in the right part of the image the clear hole where the mRNA must come in and out from, I guess:

Figure four of their article shows the full mechanism they propose for the process of mRNA decay as a four step process of Binding, Hydrolysis, Thermal Breathing, and Translocation.

McCown, Roth and Breaker @ Yale
More glmS ribozymes identified via sequence-structural consensus and with the addition of this ones a new (refined) consensus is suggested.
RNA, 17, 728-736 (2011)
By using the infernal software which looks at sequence consensus and secondary structure consensus they identify more possible candidates for a type of ribozyme. This ribozyme is called glmS, and it's found in prokaryotes.
It seems like this ribozyme is located at the 5' un-translated region (UTR), of mRNA, but, it does assume a 3D-fold. Targeting this ribozyme with antibacterial drugs might result in the control of expression of peptidoglycan and extracellular lipopolysaccharides, which, I'm guessing, must be essential for having a functional prokaryote bacteria.
In general, the article goes along the main proposal or idea of Breaker that there are many 3D structured RNA's that we still don't know much about.

Fang, Yoffe, Gelbart, and Ben-Shaul @ UCLA and Hebrew Uni @ Jerusalem
Another secondary structure folding algorithm where sequential folding starts after locating the duplex (base-pair) which results on the largest possible single stranded loops.
J. Phys. Chem. B, XX, XX-XX (2011)
Perhaps the best way to describe this new algorithm for secondary structure prediction is by using their main figure reproduced here:

Tuesday, March 1, 2011

Weekly RNA News - Week IX - March 2011

Mackay @ U. Sidney, Font and Segal @ UCDavis
The Prospects for Designer Single-stranded RNA-binding Proteins (RBP)
Nature Structure and Molecular Bio., 18, 256-261 (2011)
There are an array of possible uses that RNA-binding proteins could be engineered for. The following figure in their publication makes a nice review of such possibilities.

In their review they show that there are mainly four classes of RBP's. They are called RNA recognition motifs (RRM), Pumilio repeat domains (PUF), human heterogeneous nuclear ribonucleoprotein K homology (KH), and zinc-fingers (ZF). Of these proteins so far the most efficient in recognition are the PUF ones, but the authors point out that this might be due to the infancy of the field.
They also mention the possibility of having proteins that bind to double-stranded RNA's, like the ones present in viruses and in the "new" RNA world of small interfering RNA's and micro RNA's, but focus their attention on single stranded RNA binding, which makes sense if one wants to target mRNA.
I find this review very interesting since in the greater sense it implicitly says that this is a way to bring back the game to proteins. Just by looking at their very neat figure for possible protein-ssRNA interactions one just can't help to wonder that the yellow blob, instead of being a protein, could be an RNA, a DNA, a PNA, or a modified nucleic acid.