TMEM126A is a mitochondrial located mRNA (MLR) protein of the mitochondrial inner membrane

Background

Hereditary optic neuropathies (HONs) are a heterogeneous group of disorders that affect retinal ganglion cells (RGCs) and axons that form the optic nerve. Leber's Hereditary Optic Neuropathy and the autosomal dominant optic atrophy related to OPA1 mutations are the most common forms. Nonsyndromic autosomal recessive optic neuropathies are rare and their existence has been long debated. We recently identified the first gene responsible for these conditions, TMEM126A. This gene is highly expressed in retinal cellular compartments enriched in mitochondria and supposed to encode a mitochondrial transmembrane protein of unknown function.

Methods

A specific polyclonal antibody targeting the TMEM126A protein has been generated. Quantitative fluorescent in situ hybridization, cellular fractionation, mitochondrial membrane association study, mitochondrial sub compartmentalization analysis by both proteolysis assays and transmission electron microscopy, and expression analysis of truncated TMEM126A constructs by immunofluorescence confocal microscopy were carried out.

Results

TMEM126A mRNAs are strongly enriched in the vicinity of mitochondria and encode an inner mitochondrial membrane associated cristae protein. Moreover, the second transmembrane domain of TMEM126A is required for its mitochondrial localization.

Conclusions

TMEM126A is a mitochondrial located mRNA (MLR) that may be translated in the mitochondrial surface and the protein is subsequently imported to the inner membrane. These data constitute the first step toward a better understanding of the mechanism of action of TMEM126A in RGCs and support the importance of mitochondrial dysfunction in the pathogenesis of HON.

General significance

Local translation of nuclearly encoded mitochondrial mRNAs might be a mechanism for rapid onsite supply of mitochondrial membrane proteins.     

Ecological significance of seed desiccation sensitivity in Quercus ilex

Background and Aims

Several widespread tree species of temperate forests, such as species of the genus Quercus, produce recalcitrant (desiccation-sensitive) seeds. However, the ecological significance of seed desiccation sensitivity in temperate regions is largely unknown. Do seeds of such species suffer from drying during the period when they remain on the soil, between shedding in autumn and the return of conditions required for germination in spring?

Methods

To test this hypothesis, the Mediterranean holm oak (Quercus ilex) forest was used as a model system. The relationships between the climate in winter, the characteristics of microhabitats, acorn morphological traits, and the water status and viability of seeds after winter were then investigated in 42 woodlands sampled over the entire French distribution of the species.

Key Results

The percentages of germination and normal seedling development were tightly linked to the water content of seeds after the winter period, revealing that in situ desiccation is a major cause of mortality. The homogeneity of seed response to drying suggests that neither intraspecific genetic variation nor environmental conditions had a significant impact on the level of desiccation sensitivity of seeds. In contrast, the water and viability status of seeds at the time of collection were dramatically influenced by cumulative rainfall and maximum temperatures during winter. A significant effect of shade and of the type of soil cover was also evidenced.

Conclusions

The findings establish that seed desiccation sensitivity is a key functional trait which may influence the success of recruitment in temperate recalcitrant seed species. Considering that most models of climate change predict changes in rainfall and temperature in the Mediterranean basin, the present work could help foresee changes in the distribution of Q. ilex and other oak species, and hence plant community alterations.     

Comparison Between poly(dG-dC)·poly(dG-dC) and DNA Modified by cis-diamminedichloroplatinum (II): Immunological and Spectroscopic Studies

Abstract

The importance of the base composition and of the conformation of nucleic acids in the reaction with the drug cis-diamminedichloroplatinum(II) has been studied by competition experiments between the drug and several double-stranded polydeoxyribonucleotides. Binding to poly(dG)·poly(dC) is larger than to poly (dG-dC)·poly(dG-dC). There is no preferential binding in the competition between poly(dG-dC) ·poly(dG-dC), poly(dA-dC) ·poly(dG-dT) and poly(dA-dG)·poly(dC-dT). In the competition between poly(dG-dC) ·poly (dG-dC) (B conformation) and poly(dG-br⁵dC) ·poly(dG-br⁵dC) (Z conformation), the drug binds equally well to both polynucleotides. In natural DNA, modification of guanine residues in (GC)_n·(GC)_nsequences by the drug has been revealed by the inhibition of cleavage of these sequences by the restriction enzyme BssHII. By means of antibodies to platinated poly(dG-dC), it is shown that some of the adducts formed in platinated poly(dG-dC) are also formed in platinated pBR322 DNA. The type of adducts recognized by the antibodies is not known. Thin layer chromatography of the products after chemical and enzymatic hydrolysis of platinated poly(dG-dC) suggests that interstrand cross-links are formed. Finally, the conformations of poly(dG-m⁵dC) modified either by cis-diamminedichloroplatinum(II) or by trans-diammine- dichloroplatinum(II) have been compared by circular dichroism. Both the cis-isomer and the trans-isomer stabilize the Z conformation when they bind to poly(dG-m⁵dC) in the Z conformation. When they bind to poly(dG-m⁵dC) in the B conformation, the conformations of poly(dG-m⁵dC) modified by the cis or the trans-isomer are different. Moreover, the cis-isomer facilitates the B form-Z form transition of the unplatinated regions while the trans-isomer makes it more difficult.     

Circulation of whale-bone artifacts in the northern Pyrenees during the late Upper Paleolithic

The importance of coastal resources in the late Upper Paleolithic of western Europe has been reevaluated in recent years thanks to a growing body of new archeological evidence, including the identification of more than 50 implements made of whale bone in the Magdalenian level of the Isturitz cave (western Pyrenees). In the present study, the assemblages of osseous industry from 23 Magdalenian sites and site clusters in the northern Pyrenees were investigated, systematically searching for whale-bone implements. The objective of this research was to determine if, and how, tools and weapons of coastal origin were circulated beyond Isturitz into the inland, and if similar implements existed on the eastern, Mediterranean side of the Pyrenees. A total of 109 whale-bone artifacts, mostly projectile heads of large dimensions, were identified in 11 sites. Their geographic distribution shows that whale bone in the Pyrenean Magdalenian is exclusively of Atlantic origin, and that objects made of this material were transported along the Pyrenees up to the central part of the range at travel distances of at least 350 km from the seashore. This phenomenon seems to have taken place during the second half of the Middle Magdalenian and the first half of the Late Magdalenian, ca. 17,500–15,000 cal BP (calibrated years before present). The existence of a durable, extended coastal-inland interaction network including the circulation of regular tools is thus demonstrated. Additionally, differences between the whale-bone projectile heads of the Middle Magdalenian and those of the Late Magdalenian document an evolutionary process in the design of hunting weapons.     

Efficient homologous recombination with short length flanking fragments in Ku70 deficient Yarrowia lipolytica strains

In Yarrowia lipolytica, targeted gene replacement occurs only with long length (1 kb) homologous flanking fragments, as this yeast preferentially uses the non-homologous end-joining mechanism (NHEJ) for DNA repair over homologous recombination (HR). To improve the frequency of HR, we identified and disrupted the KU70 and KU80 genes responsible for double strand break repair in the NHEJ pathway in Y. lipolytica. In ku70? HR of URA3 marker at the ADE2 locus occurred with 43 % frequency with as little as 50 bp long flanking regions. The number of Ura⁺ transformants was reduced to 1 % of the Po1d (ura3-302) wild type-like strain level, regardless of the flanking fragment length. On the contrary, even though HR was not improved in ku80?, Ura⁺ transformants was 60 % lower compared to the wild type.     

Mus in Morocco: a Quaternary sequence of intraspecific evolution

North Africa is an intricate biogeographical region at the crossroads of immigration waves from tropical Africa and Asia. Species confined between various barriers (Atlas Mountains, arid environments such as the Sahara in the south, water masses such as the Mediterranean Sea in the north, and the Atlantic Ocean in the west) were generally forced to adapt locally to environmental changes instead of tracking their habitat by shifting their distribution area. The present study aims at providing first insight into the evolution of the genus Mus, and more specifically of the western Mediterranean species Mus spretus in this area. The study relies on the abundant Late Pleistocene and Middle Holocene fossil assemblage from the El Harhoura 2 cave (Rabat‐Témara, Morocco). This exceptional record was studied using geometric morphometrics applied to first upper and lower molars, constituting the most informative and best preserved fossil remains for such small rodents. Two main issues were addressed. (1) Geometric morphometrics was used to clarify taxonomic status and phylogenetic relationships among fossil and modern species in this area. Morphometric analysis revealed good discrimination of most modern and fossil species but failed to document intermediate forms tracing anagenetic evolution. Not mutually exclusive, the occurrence of complex processes of morphological evolution in this genus such as parallel evolution and the action of stabilizing selection may make it difficult to translate patterns of morphological evolution into phylogenetic conclusions. (2) The record was shown to document a sequence of intraspecific evolution of M. spretus. The morphology of the molars through the fossil record of El Harhoura 2 was surprisingly stable despite extensive modern variation. The limited temporal variation largely failed to correlate to palaeoenvironmental proxies. The mouse fossil record at El Harhoura 2 thus presents an intriguing case of morphological stasis despite extensive environmental changes. This long‐term stability may have been recently perturbed by anthropogenic factors including landscape changes and introduction of various competitors and predators, leading to a size reduction. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 599–621.     

New insights into the ear region anatomy and cranial blood supply of advanced stem Strepsirhini: Evidence from three primate petrosals from the Eocene of Chambi,Tunisia

We report the discovery of three isolated primate petrosal fragments from the fossiliferous locality of Chambi (Tunisia), a primate-bearing locality dating from the late early to the early middle Eocene. These fossils display a suite of anatomical characteristics otherwise found only in strepsirhines, and as such might be attributed either to Djebelemur or/and cf. Algeripithecus, the two diminutive stem strepsirhine primates recorded from this locality. Although damaged, the petrosals provide substantial information regarding the ear anatomy of these advanced stem strepsirhines (or pre-tooth-combed primates), notably the patterns of the pathway of the arterial blood supply. Using μCT-scanning techniques and digital segmentation of the structures, we show that the transpromontorial and stapedial branches of the internal carotid artery (ICA) were present (presence of bony tubes), but seemingly too small to supply enough blood to the cranium alone. This suggests that the ICA was not the main cranial blood supply in stem strepsirhines, but that the pharyngeal or vertebral artery primitively ensured a great part of this role instead, an arterial pattern that is reminiscent of modern cheirogaleid, lepilemurid lemuriforms and lorisiforms. This could explain parallel loss of the ICA functionality among these families. Specific measurements made on the cochlea indicate that the small strepsirhine primate(s) from Chambi was (were) highly sensitive to high frequencies and poorly sensitive to low frequencies. Finally, variance from orthogonality of the plane of the semicircular canals (SCs) calculated on one petrosal (CBI-1-569) suggests that Djebelemur or cf. Algeripithecus likely moved (at least its head) in a way similar to that of modern mouse lemurs.