Novelty in the polyadenylation machinery

Late last fall, I published a short review in WIRES RNA that discussed some curious findings coming out of the growing community of plant scientists whose research touches on mRNA polyadenylation. When we think about the polyadenylation machinery, it is reflexive to consider that the core subunits (the CPSF, CstF, CFIm, and CFIIm subunits) should be essential. Indeed, this is the case in yeast and mammals, as far as one can tell. It is thus very surprising that Arabidopsis is able to grow (sometimes, with almost imperceptible phenotypes) in the absence of several supposedly core subunits. The list of dispensable proteins in plants includes CPSF30, FIP1, CstF77, and CstF64.

While in Lexington …

… for the recently-started Spring Meet at Keeneland (it really is this pretty), I suggest that you find time to attend the 2013 Naff Symposium at the University of Kentucky. This is an annual event put on by the Dept. of Chemistry and centers on aspects of chemistry and molecular biology. This year’s topic is The Origin of Life, and the line-up of speakers is pretty amazing.

Videos …

A while ago,  I posted about an interesting virtual meeting on the ribosome.  Somewhat belatedly, I can point to a link to videos of the talks.  Lots of good stuff.  Enjoy.

(HT to Paul Nelson.)

Don’t miss this!

Back in November, there was a fascinating workshop on subjects pertaining to he origins of life.  Some of the talks dealt with structural and evolutionary aspects of ribosomes.  Next week, there will be a two-day symposium that follows up, in a sense, on this workshop.  The symposium is entitled “The Ribosome: Structure, Function & Evolution”.  The really great thing is that, like the workshop in November, this symposium can be “attended” over the internet.  So you have no excuses for missing this event.

And it promises to be a good one.  Here is the list of speakers, taken from the program here:

 

Darwin Lecture 2011

This year’s Darwin Week festivities in the Lexington area featured a talk by Jack Horner.  It was part science and part entertainment, very well attended.  (The organizers must have remembered Horner’s last visit to Lexington,  when the room he spoke in was overflowing, and probably as many people were outside as in the hall.  This time, the main hall of the Singletary Center was used, and it was pretty full.)

The talk itself had its highlights and low points.  I found Horner’s discussion of his “dissection” of fossilized dinosaur bones to be riveting, and I think his mock “extinction” of dinosaur species (actually, the revision of the fossil record so as to recognize that many supposed species are probably just juvenile versions of the same species) was presented in a clever and accessible fashion.

The stuff about the “chickenosuarus”?  Not so much.  I’m not sure about the idea of telling a generation of elementary and middle schoolers (a large and rapt part of the audience) that we’re going to be able to modify chickens so that they will have dinosaur-like tails, “hands”, and teeth, all in about 5 years or so.  I couldn’t tell if he really believed this or not – he’s a pretty good showman and has a knack for drawing the younger members of the audience into the subject.  But if he does, well, um, no.  (To paraphrase what I suspect would be my daughters’ reaction.)

I’ll admit that this talk was a bit more special for me, since it gave me an excuse to spend some time with my older daughter, Heather.  She’s back in the area, and was able to get back to Lexington to attend the talk (and actually be an usher for the event).  A nice dinner at Banana Leaf and some back-and-forth about the subjects (Heather giving me some inside scoop from the perspective of an MSU grad student, and me panning the chickenosaurus schtick) made for a fun time.

REM

No, it’s not about the rock band.  Nor is it about sleep physiology.  Rather, this short blurb is intended to point out a recent review in Trends in Biochemical Sciences that ties together a long trickling of research extend back for many decades.

For at least 20 years, it has been known that a number of enzymes that catalyze reactons in intermediary metabolic pathways are also RNA binding proteins.  The “classical” case is that of aconitase.  This enzyme catalyzes the isomerization of citrate to isocitrate, a reaction that is part of the tricarboxylic acid cycle.  The enzyme also binds the so-called iron-responsive element in mRNAs, and in so doing regulates RNA stability and translation.  Aconitase activity and RNA binding are mutually exclusive, and the role the protein plays depends on teh iron status of the cell.

Similar RNA-binding moonlighting has since been shown for a number of other enzymes.  I won’t list them here – the review does a nice job of this.  The review also discusses the possible integration of metabolic cues with RNA homeostasis.  It doesn’t touch on a more fascinating topic – the possibility that RNA binding may be a vestige of the deep past, reflecting the possibility that, at one time, all proteins may have interacted with RNA or been involved with RNA metabolism in some way.  But the latter is a subject that better left for another review.

Signature in the Cell?

There is much abuzz in the ID-o-sphere regarding Stephen Meyer’s new book, “Signature in the Cell: DNA and the Evidence for Intelligent Design”.  The book is a lengthy recapitulation of the main themes that ID proponents have been talking about for the past 15 years or so; indeed, there will be precious little that is new for seasoned veterans of the internet discussions and staged debates that have occurred over the years.

Long though the book is, it is built around one central theme – the idea that the genetic code harbors evidence for design.  Indeed, the genetic code – the triplet-amino acid correspondence that is seen in life – is the “Signature in the Cell”.  Meyer contends that the genetic code cannot have originated without the intervention of intelligence, that physics and chemistry cannot on their own accords account for the origin of the code.

It is this context that a recent paper by Yarus et al. (Yarus M, Widmann JJ, Knight R, 2009, RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code, J Mol Evol  69:406–429) merits discussion.  This paper sums up several avenues of investigation into the mode of RNA-amino acid interaction, and places the body of work into an interesting light with respect to the origin of the genetic code.  The bottom line, in terms that relate to Meyer’s book, is that chemistry and physics (to use Meyer’s phraseology) can account for the origin of the genetic code.  In other words, the very heart of Meyer’s thesis (and his book) is wrong.

Plant Poly(A) Polymerases

Among the conserved proteins of the polyadenylation complex, seen in all eukaryotes (including the highly-reduced polyadenylation complex in Giardia) is the enzyme that adds the poly(A) tail – polynucleotide adenylyltransferase or, more colloquially, poly(A) polymerase.  One would think that the evolutionary history of such a core component of the gene expression machinery would be rather unremarkable – it should be present at the outset and pretty much conserved throughout evolutionary history.

Of course, reality is much more interesting.  A former student of mine did her thesis on Arabidopsis poly(A) polymerases, characterizing the four (4!) genes and the protein isoforms.  A former postdoc in the lab had done some work in rice poly(A) polymerase genes, and found an equally interesting multiplicity of genes as well as some fascinating expression characteristics.  This work has been recently published in PLoS ONE; as is my custom, this post is intended to point out the paper and invite (here or at the journal’s site for the paper) comment, discussion, and criticism.

A brief recap and one or two of the more provocative findings:

It’s all about ribosomes

What is all about ribosomes?  Undoubtedly, readers will quickly make the connection between the title of this short essay and the recent awarding of the 2009 Nobel Prize in Chemistry to three whose work has centered on the ribosome.  The Nobel prize announcement emphasized the links between ribosomes and antibiotics, rightly focusing attention on the fact that many antibiotics target the bacterial ribosome, different as it is from its eukaryotic (cytosolic) counterpart in important ways.  What I want to do is to ramble on about some other aspects of ribosomes that I find fascinating.  Hopefully, by turning some features of biology on their heads, readers will think differently about genomes, gene expression, and other facets of molecular biology.

“Where Did All the Flowers Come From?”

Carl Zimmer has a good article in the NY Times entitled “Where Did All the Flowers Come From?”   The article summarizes lots of interesting stuff, but I find the speculation regarding the evolution of the endosperm to be particularly though-provoking.  Of course, anytime one mentions genome duplication to me, visions of gene silencing and small RNAs begin dancing in my mind.  A recent article from David Baulcombe’s group merits mention in this context.  This paper describes a developmental study of RNA polymerase IV-derived small interfering RNAs (siRNAs).  The remarkable finding in this paper is the observation that the synthesis of many polIV-derived siRNAs is initated at the onset of the development of the maternal gametophyte, and that these siRNAs are in turn derived from the maternal genome(s) in the endosperm.  This has ramifications for the expression of the different genomes in the endosperm, for genome imprinting, and likely for the evolution of flowers and seed development in plants.

The abstract from the paper:

“Most eukaryotes produce small RNA (sRNA) mediators of gene silencing that bind to Argonaute proteins and guide them, by base pairing, to an RNA target. MicroRNAs (miRNAs) that normally target messenger RNAs for degradation or translational arrest are the best-understood class of sRNAs. However, in Arabidopsis thaliana flowers, miRNAs account for only 5% of the sRNA mass and less than 0.1% of the sequence complexity. The remaining sRNAs form a complex population of more than 100,000 different small interfering RNAs (siRNAs) transcribed from thousands of loci^{1, 2, 3, 4, 5}. The biogenesis of most of the siRNAs in Arabidopsis are dependent on RNA polymerase IV (PolIV), a homologue of DNA-dependent RNA polymerase II^{2, 3, 6}. A subset of these PolIV-dependent (p4)-siRNAs are involved in stress responses, and others are associated with epigenetic modifications to DNA or chromatin; however, the biological role is not known for most of them. Here we show that the predominant phase of p4-siRNA accumulation is initiated in the maternal gametophyte and continues during seed development. Expression of p4-siRNAs in developing endosperm is specifically from maternal chromosomes. Our results provide the first evidence for a link between genomic imprinting and RNA silencing in plants.”

The citation:

Mosher RA, Melynk CW, Kelly KA, Dunn RM, Studholme DJ, Baulcombe DC. 2009.  Uniparental expression of PolIV-dependent siRNAs in developing endosperm of Arabidopsis. Nature 460, 283-286 (9 July 2009) | doi:10.1038/nature08084.