Catálogo de publicaciones - revistas

<jats:title>RNA Structural Principles Revealed</jats:title> <jats:p> The thermodynamic principles that link RNA primary and secondary structure are well understood, but the relation to tertiary structure is unclear. To gain insight, <jats:bold> Bailor <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="202" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1181085">202</jats:related-article> ) analyzed all available three-dimensional structures of an important RNA motif, the two-way junction, and found that flanking helices sample only a small percentage of possible interhelical orientations. They identified a set of general rules for the relative orientation of helices as a function of the size of the interconnecting junction. The results also rationalize how ligands stabilize specific conformations. Understanding the topological constraints that define RNA global conformation and dynamic adaptation provides guiding principles for rational manipulation of RNA structure. </jats:p>

<jats:title>Dissecting TFIIB Mechanics</jats:title> <jats:p> Eukaryotic RNA polymerase II (Pol II) requires five protein cofactors for promoter recognition and initiation of transcription. The factor TFIIB is implicated in start site selection and stabilization of the initial transcript. The co-crystal structure of Pol II and TFIIB showed an N-terminal “finger” region located in the RNA exit channel, but the core C-terminal region of TFIIB was disordered. Now <jats:bold> Liu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="206" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1182015">206</jats:related-article> ; published online 12 November) present a structure of the same complex determined under different conditions in which the C-terminal structure is well localized but the finger is disordered. Docking DNA into the structure suggests that the C-terminal region stabilizes initial promoter melting. After transcription of a few bases, TFIIB probably switches to the alternate conformation where the C-terminal region is released and the finger region stabilizes the initial transcript. </jats:p>

<jats:title>Niche Metamorphosis</jats:title> <jats:p> The gut epithelium is continually renewed by cells generated from intestinal stem cells. In the fruit fly <jats:italic>Drosophila</jats:italic> , cells of the adult gut are derived from cells set aside before metamorphosis. <jats:bold> Mathur <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="210" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1181958">210</jats:related-article> ) now show that an early asymmetric cell division in larval stages establishes a niche that encloses a proliferating group of undifferentiated stem cells. At metamorphosis, the niche breaks down and the stem cells are freed. Most of them differentiate into adult gut progenitors, but a minority takes on the task of establishing a new, adult, stem cell niche with more liberal operating rules. </jats:p>

<jats:title>Cocaine Addiction and Histone Methylation</jats:title> <jats:p> Long-lasting behavioral syndromes associated with chronic cocaine exposure may result from dysregulation of the global transcriptional machinery. <jats:bold> Maze <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="213" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1179438">213</jats:related-article> ) observed that histone lysine methylation in the nucleus accumbens plays a critical role in mediating the regulation of gene expression in response to repeated cocaine self-administration. Chronic cocaine was linked to overall reductions in dimethylation of lysine 9 of histone 3 (H3K9) in this brain region. Repressing H3K9 after chronic cocaine administration facilitated reward-related changes in behavior. The authors identifed the methyltransferase G9a as an essential mediator and an important regulator of dendritic spine plasticity. Downregulation of G9a was linked to the transcription factor ΔFosB. </jats:p>

<jats:title>Ratting Out a Diabetes Gene</jats:title> <jats:p> Inbred animals with inherited susceptibility to disease can be especially informative regarding pathogenetic mechanisms because they carry naturally occurring genetic variants of the same type that cause disease in humans. This principle is illustrated by <jats:bold> Rosengren <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="217" related-article-type="in-this-issue" vol="327" xlink:href="10.1126/science.1176827">217</jats:related-article> ; published online 19 November), whose analysis of an inbred strain of rats prone to develop type 2 diabetes led to the discovery of a gene whose aberrant overexpression suppresses pancreatic insulin secretion in both rats and humans. The culprit gene, ADRA2A, encodes the alpha2A adrenergic receptor and is potentially a valuable lead for diabetes therapy because it can be targeted pharmacologically. </jats:p>

<jats:p>The show includes how cocaine alters gene expression, third-party punishment in fish, and working towards simpler, cheaper particle accelerators.</jats:p>

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