e hënë, dhjetor 12, 2005

One Residue, Two Functions

The ETS family of transcription factors plays a variety of roles in development and differentiation. All members of the family have a highly conserved DNA-binding domain. In addition to binding to DNA, several members of the ETS family interact with other DNA-binding proteins, including members of the basic leucine zipper (bZIP) family. However, the molecular basis for this interaction has remained elusive.

Using Spi-1, one of the more diverse members of the ETS family, James A. Listman and colleagues demonstrated a novel mode of interaction for the ETS family transcription factors with the bZIP family of transcription factors. The authors convincingly showed that an arginine residue in Spi-1 that is essential for nuclear localization and corresponding DNA binding is also utilized for interaction with bZIP domains. These observations suggest new mechanisms of protein-protein and protein-DNA interactions for transcription factors. More...

e hënë, gusht 08, 2005

Here a Splice, There a Splice, Everywhere a Splice Splice

Approximately 60% of human genes undergo alternative splicing. This alternative splicing allows a single gene to encode dozens, and in some cases even thousands, of different protein isoforms, vastly increasing the diversity of the proteome that can be encoded by a limited number of genes. In mammals, only a fraction of the regulatory proteins (splicing factors) involved in controlling alternative splicing have been identified, and little is known about the mechanisms by which these factors regulate splicing. In this paper, Naganari Ohkura and colleagues identify an enzyme called coactivator-associated arginine methyltransferase 1 (CARM1), which is known to contribute to transcriptional activation by methylating histone H3, as a regulator of alternative splicing.

Ohkura and colleagues offer two novel observations about CARM1: 1) they identify new splicing variants of CARM1, which are expressed in a tissue-specific manner, and 2) they report the exciting discovery that one of the new splicing variants, CARM1-v3, binds to the U1 small nuclear ribonucleoprotein particle (snRNP) component of the spliceosome and alters splicing patterns of mRNAs. Interestingly, a C-terminal CARM1-v3 region, which is unique to this particular splice variant, is responsible for the splicing regulation function, whereas the methyltransferase activity of CARM1 is dispensable. These findings add CARM1 to the list of components that can modulate 5' splice site selection and provide a new mechanism by which transcription and processing, two critical steps in gene expression, may be coordinated.

Luck of the Draw

Nat. Genet. 10.1038/ng1608 (2005). Genetically identical organisms that have been raised in identical environments age at different rates, suggesting that in addition to genes and environment, chance physiological phenomena can influence life span. Rea et al. report that the stress response system of Caenorhabditis elegans is subject to an underlying physiological randomness that affects how it copes with environmental insults. They placed the gene encoding green fluorescent protein (GFP) under the control of the regulatory region from the gene encoding a heat shock protein, creating an easily scored biomarker. Upon exposure to heat, isogenic worms exhibited considerable variation in fluorescence, and those expressing the highest amount of GFP tolerated heat the best and lived the longest. The physiological state indexed by GFP expression level was not heritable, and the authors suggest that stochastic variation in molecular and biochemical reactions could account for the variation in individual robustness and longevity. -- LDC

Activating AMP-Activated Protein Kinase without AMP

The cellular mechanisms for dealing with nutritional stress are remarkably conserved, with the same signaling network used in organisms from yeast to mammals. In one sense, this is not terribly surprising since the most pressing response to such potential injury is always the same: suppress those biochemical reactions that consume energy while at the same time triggering those metabolic pathways most effective at generating ATP. But an interesting problem to contemplate is how this fundamental process has been adapted to the complexities of a multicellular organism in which recognition of the nutritional state is frequently provided by more subtle cues such as hormones or impulses generated within the central nervous system. Moreover, although the cellular responses to nutrient deprivation are conserved phylogenetically, organismal reactions in metazoans are more multifaceted in that one organ often sacrifices for the good of the whole. The major phylogenetically conserved pathway for signaling nutritional stress is now well established as centering on the protein kinase Snf1 in budding yeast, which is orthologous to AMPK-activated protein kinase (AMPK) in higher organisms. As its name suggests, mammalian AMPK is regulated by changes in the ratio of AMP to ATP, a sensitive indicator of the energy state of the cell. Now, three papers report the intriguing observation that an alternative pathway mediated by a Ca2+-dependent protein kinase is also capable of regulating AMPK (Hawley et al., 2005, Hurley et al., 2005 and Woods et al., 2005).

e martë, qershor 28, 2005

Aron A, Fisher HE, Mashek DJ, Strong G, Li HF, Brown LL.

Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. It has an important influence on social behaviors that have reproductive and genetic consequences. To determine which reward and motivation systems may be involved, we used functional magnetic resonance imaging and studied 10 women and 7 men who were intensely "in love" from 1-17 months. Participants alternately viewed a photograph of their beloved and a photograph of a familiar individual, interspersed with a distraction-attention task. Group activation specific to the beloved under the two control conditions occurred in dopamine-rich areas associated with mammalian reward and motivation, namely the right ventral midbrain and three regions of the right caudate nucleus. Activation in the left ventral tegmental area was correlated with facial attractiveness scores. Activation in the right medial caudate was correlated with questionnaire scores that quantified intensity of romantic passion. In the left insula-putamen-globus pallidus, activation correlated with trait affect intensity. The results suggest that romantic love uses subcortical reward and motivation systems to focus on a specific individual, that limbic cortical regions process individual emotion factors, and that there is localization heterogeneity for reward functions in the human brain.

e hënë, qershor 27, 2005

Which expert should I believe?

As a reader of this journal you are probably a professional scientist with an interest in communicating the importance of what you do to the world at large. We share that interest, and advertise to journalists the work we publish that we feel most likely to be of general interest, via press releases on the EurekAlert! website. This works very well, and papers in Current Biology are frequently covered in the general media.

This is all fine and dandy; good for us, our authors, the science journalists and their readers.... There is an aspect of this process that is, I believe, deadly serious and of the utmost importance. In certain areas of science, public understanding has an influence on behaviour with serious consequences — this is especially true of medical and environmental matters.

e premte, qershor 24, 2005

Structure, function, and evolution of the tRNA endonucleases of Archaea: An example of subfunctionalization

We have detected two paralogs of the tRNA endonuclease gene of Methanocaldococcus jannaschii in the genome of the crenarchaeote Sulfolobus solfataricus. This finding has led to the discovery of a previously unrecognized oligomeric form of the enzyme. The two genes code for two different subunits, both of which are required for cleavage of the pre-tRNA substrate. Thus, there are now three forms of tRNA endonuclease in the Archaea: a homotetramer in some Euryarchaea, a homodimer in other Euryarchaea, and a heterotetramer in the Crenarchaea and the Nanoarchaea. The last-named enzyme, arising most likely by gene duplication and subsequent "subfunctionalization," requires the products of both genes to be active.