Sequence composition similarities with the 7SL RNA are highly predictive of functional genomic features

Transposable elements derived from the 7SL RNA gene, such as Alu elements in primates, have had remarkable success in several mammalian lineages. The results presented here show a broad spectrum of functions for genomic segments that display sequence composition similarities with the 7SL RNA gene. Using thoroughly documented loci, we report that DNaseI-hypersensitive sites can be singled out in large genomic sequences by an assessment of sequence composition similarities with the 7SL RNA gene. We apply a root word frequency approach to illustrate a distinctive relationship between the sequence of the 7SL RNA gene and several classes of functional genomic features that are not presumed to be of transposable origin. Transposable elements that show noticeable similarities with the 7SL sequence include Alu sequences, as expected, but also long terminal repeats and the 5′-untranslated regions of long interspersed repetitive elements. In sequences masked for repeated elements, we find, when using the 7SL RNA gene as query sequence, distinctive similarities with promoters, exons and distal gene regulatory regions. The latter being the most notoriously difficult to detect, this approach may be useful for finding genomic segments that have regulatory functions and that may have escaped detection by existing methods.     

Interaction between the tRNA-Binding and C-Terminal Domains of Yeast Gcn2 Regulates Kinase Activity In Vivo

The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2α. Gcn2 is activated in amino acid-deprived cells by binding of uncharged tRNA to the regulatory domain related to histidyl-tRNA synthetase, but the molecular mechanism of activation is unclear. We used a genetic approach to identify a key regulatory surface in Gcn2 that is proximal to the predicted active site of the HisRS domain and likely remodeled by tRNA binding. Mutations leading to amino acid substitutions on this surface were identified that activate Gcn2 at low levels of tRNA binding (Gcd^- phenotype), while other substitutions block kinase activation (Gcn^- phenotype), in some cases without altering tRNA binding by Gcn2 in vitro. Remarkably, the Gcn^- substitutions increase affinity of the HisRS domain for the C-terminal domain (CTD), previously implicated as a kinase autoinhibitory segment, in a manner dampened by HisRS domain Gcd^- substitutions and by amino acid starvation in vivo. Moreover, tRNA specifically antagonizes HisRS/CTD association in vitro. These findings support a model wherein HisRS-CTD interaction facilitates the autoinhibitory function of the CTD in nonstarvation conditions, with tRNA binding eliciting kinase activation by weakening HisRS-CTD association with attendant disruption of the autoinhibitory KD-CTD interaction.     

Patterns and sources of variation in Daphnia phosphorus content in nature

It has recently been shown that Daphnia can vary in the phosphorus (P)-content of their body tissues, but the relative importance of genetic versus environmental causes for this variation is unexplored. We measured variation in P-content (as % body mass) of Daphnia from eight lakes and conducted experiments to contrast three sources of variation: interspecific variation, clonal variation and phenotypic plasticity. Daphnia P-content decreased with increasing seston C:P ratio across lakes. This relationship reflected both inter- and intraspecific variation. Daphnia parvula and D. dubia exhibited high P-content and were found in shallow lakes with low C:P seston, whereas D. pulicaria had low P-content and was found in deep, stratified lakes having high C:P seston. Populations of D. dentifera spanned this lake gradient and exhibited P-content that was negatively related to seston C:P. Evidence for phenotypic plasticity came from experiments with D. pulicaria and D. dentifera collected from a lake with P-deficient seston and fed a P-sufficient diet in the laboratory. In addition, populations of D. dentifera differed in P-content even after 7 d of feeding on P-sufficient resources, suggesting within-species clonal variation. However, mesocosm experiments revealed broad and surprisingly continuous variation in the P-content of individual clones of D. pulex (range 1.54–1.05%) and D. mendotae (1.51–1.07%) over a gradient in dietary C:P. The broad range in P-content exhibited by individual clones, acclimated for generations, suggests that variation in Daphnia P-content from laboratory experiments needs to be interpreted with caution. These results also show that phenotypic variation in response to environment can be a larger source of variation in P-content than genetic differences within or among species.     

Book reviews

Environmental Biology of Fishes -     

Platinum(II) binding to metallothioneins

The reaction of equine renal metallothionein (MT) with excess K2PtCl4 at pH 2 results in a polymeric adduct containing 17 +/- 2 mol Pt/mol MT. A monomeric adduct containing 7 mol Pt/mol MT is obtained at neutral pH. Rates of reaction of Pt7MT with DTNB and iodoacetic acid are consistent with Pt2+ to cysteine thiolate coordination, and the extent of reaction in both cases is 11 +/- 2 mol cys/mol MT. Adducts from the reaction of K2PtCl4 with apoMT chemically modified at the N-terminal methionine residue, Cd7MT, and native MT are also reported. A structural model of Pt7MT is proposed in which the square planar tetrathiolate Pt(II) unit is incorporated into a three-metal beta cluster. Implications for the metabolism of platinum anticancer drugs are discussed.     

Neuroleptic-like electroencephalographic changes in schizophrenics through biofeedback

Nine schizophrenic patients participated in a study which explored whether EEG feedback techniques could effect changes in the EEG similar to those associated with neuroleptic-induced improvement. During five sessions, each patient was presented feedback signals which continuously refected the discrepancy between characteristics of the patient's EEG power spectral profile and spectral profile characteristics associated by past research with neuroleptic induced clinical improvement. Significant within-session changes were observed for two of three EEG power spectrum bands of interest. No significant session-to-session EEG changes were observed. The results suggest that the EEG of schizophrenics can be temporarily altered, using feedback techniques, in a way that mimics the EEG changes that have been shown to occur with neuroleptic induced clinical improvement.The authors are indebted to Turan M. Itil, John W. Fredrickson, Michael Madwed, and Irene B. Francis. Senior authorship is shared equally.