Wednesday, February 23, 2011

Weekly RNA News - Week VIII - February 2011

Various authors and N. Ban (ETH) and J. Doudna (UCBerkeley)
Signal Recognition Particle (SRP) in complex with receptor (SR) at 3.9 Angstrom
Science, 331, 881-886 (2011)

Still an unreleased structure in the Protein Data Bank but will be coming out soon.
The Signal Recognition Particle is an RNA-protein complex which delivers at the time of translation (co-translationally) membrane and secretory proteins. The SRP is made of a surprisingly long double stranded RNA, I wonder if it stays "straight" thanks to the aid of the protein, and why would it want to do that?

A. Robbins-Pianka and M. D. Rice and M. P. Weir @ Wesleyan, Connecticut
Translation initiation sites (TIS) are influenced by secondary structure downstream and upstream of this sites in highly expressed genes.
Bioinformatics, 26, 2651-2655 (2011)

The results are clearly explained in their abstract:
"Trends in base composition and base-pairing probabilities suggest that efficient translation initiation and high protein expression are aided by reduced secondary structure upstream and downstream of the TIS. However, the downstream reduction is not observed for sets of TISs with nucleotide sequence contexts unfavorable for translation initiation, consistent with previous suggestions that secondary structure downstream of the ribosome can facilitate TIS recognition."
And in the following figure:

Monday, February 21, 2011

Weekly RNA News - Week VII - February 2011

Bujnicki Lab @ Poznan - Poland
ModeRNA python based software for RNA fold prediction.
NAR Advanced Publication. February 2011

A new software for RNA structure prediction from sequence given the existence of a structure with similar sequence is out, it's called ModeRNA and is somewhat similar to what the MC-Fold MC-Sym pipeline of Major does or the s2s, assemble "pipeline". The article has a nice up to date review on what is out there for RNA structure prediction. Published ahead of print in NAR.
You can find it online at: ModeRNA.
The last update on the software was done in november last year.

Xiao Group @ Hubei - China
Guided manual adjustment of atom clashes and atom stretches on RNA reconstruction.
JBSD 28 675-843 (2011)

Sometimes nice papers, at least from the creative point of view, go to the journals with, perhaps, not such big impact factors but strong traditions behind. I'm liking more and more some of the papers in the journal of biomolecular structure and dynamics, specially if the big shots are not the main authors. I liked the article by Zhao Y, Gong Z and Xiao Y. in JBSD 28 815-26, (2011).

Dill Group @ UCSF - USA
A so called semi-explicit solvation model which aims to be analogous in results to explicit solvation but consuming a much shorter computer time.
PNAS ahead of print February 2011

Not precisely RNA news, but an interesting method that could be applied to RNA's since it's a general solvation method.
The main idea is (coherent with Dill's group work) to think about "partition theory" type ideas, that is, we assume that the total free energy of a process can be split into additive contributions. In this case Fennell, Kehoe, and Dill propose that the free energy of solvation can be split into three components, a non-polar one, and two electrostatic polar components, one due to a first solvation shell, and the second due to the remaining bulk effect. The practical trick to do what they call semi-explicit assembly (SEA) is a four step process as clearly illustrated below:

Thursday, February 10, 2011

Weekly RNA News - Week VI - February 2011

Dekker Lab.
Nano-sized quartz cylinders for force-extension experiments.
ACS Nano. 2011 Jan 31 ahead of time.

In the Dekker lab. in the Netherlands they're now using electron beam litography to make nanometer sized cylinders and truncated cones made of quartz for use in single molecule experiments, for example for use in force extension experiments of DNA or RNA.
Dekker lab. has already provided some nice results on measurement of the persistence length of double-stranded RNA of around 640 Ångström using magnetic tweezers and compliance to the Worm-Like-Chain model.

Sarah Woodson and Eda Koculi
Review on native polyacrlyamide get electrophoresis (PAGE) on RNA.
Methods in Enzymology, Volume 469, 2009, Pages 189-208

My reviews are mainly based on what I get fed to me trough automatic periodic searches for favorite authors and topics in pubmed, and also from periodic flash reviews of the headliners related to RNA of the big journals from the US and GB. Sometimes what pubmed sends is outta sync, that is, this review is a 2009, still valid though.
It actually has some very, very, nice and simple gels which can be read in quite the clean manner. In the gel in the upper part of the image the part marked by P4-P6 refers to a catalytic RNA of the so called group I intron type, the U1 and U2 lines are constructs where the RNA sequence has been modified, that is, these are mutants. We can infer a structural change due to the sequence modification by the difference in the migration on the gel of the mutants and the original. In the lower part of the image a very interesting fact of RNA is shown, that is, RNA while folding can easily be "trapped" into intermediate folds (denoted by I) before getting to the most stable or native (denoted by N) one. We can also see that a mutated RNA (L2L5cP3) can fold faster into an "intermediate-free" lane in comparison to the wild type (wt).

It is interesting to see that in the same journal-book Dave Lilley also has some very nice experiments for what can be learned from RNA helical junctions from gels.
And not only does Sarah Woodson have the previous review but there is another one regarding OH radical footprinting in vivo using X-Ray. While refreshing what I understood of OH radical footprinting I found the following Tom Tullius quotation:

"Because the hydroxyl radical is an extremely reactive and non-discriminating free radical, the site of attack has no dependence on the base sequence of the nucleic acid. Instead, the susceptibility of a particular nucleotide to hydrogen abstraction is governed by its accessibility to solvent. This property makes the hydroxyl radical footprinting method the experimental equivalent of a calculated solvent-accessible surface area of a nucleic acid molecule"

Wednesday, February 9, 2011

Weekly RNA News - Week V - February 2011

Some weeks ago in Chemical and Engineering News there was a story about Roche pulling out of development of RNAi based drug research. Now there is a new article in C&EN talking about progress being made by some companies on RNAi, and the still latent preoccupation by RNAi pharma researchers on such a large move by Roche.
C&EN show a nice table citing the following companies having ongoing RNAi pipelines:

Marina Biotech
Silence Therapeutics

What has first impressed me greatly about these companies is the great level of their webpages. I expected older css and perhaps old flash kinda pages. But the majority of these ones look very html5 css3 like, quite stylish IMHO.

It's amazing what "good" publicity can do. If I wasn't a scientist and just wanted to invest some bucks on pharma startups, I would probably not invest in say, tekmira, which has the least "pretty" page on my superfluous 3s judgment.

Not three years have gone by since the publication of the Parisien and Major paper (Nature 1998) which, to my knowledge, is the first fully automated from sequence to 3D structure simulation of RNA, and the RNA structure prediction field sounds as if it was an already consolidated thing. There is a nice paper by Polish researchers on what there is out there and how it compares to protein folding prediction strategies. They have a table with the reviewed software and for RNA they mention RNABuilder, ModeRNA, Vfold, DMD, HiRE-RNA, MC-Fold, SimRNA, and CG. ModeRNA is the one developed by the authors of the review.