ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs.

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.

Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice.

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

Complete Mitogenome of Oreolalax Omeimontis Reveals Phylogenetic Status and Novel Gene Arrangement of Archaeobatrachia.

Species of the genus Oreolalax displayed crucial morphological characteristics of vertebrates transitioning from aquatic to terrestrial habitats; thus, they can be regarded as a representative vertebrate genus for this landing phenomenon. But the present phylogenetic status of Oreolalax omeimontis has been controversial with morphological and molecular approaches, and specific gene rearrangements were discovered in all six published Oreolalax mitogenomes, which are rarely observed in Archaeobatrachia. Therefore, this study determined the complete mitogenome of O. omeimontis with the aim of identifying its precise phylogenetic position and novel gene arrangement in Archaeobatrachia. Phylogenetic analysis with Bayesian inference and maximum likelihood indicates O. omeimontis is a sister group to O. lichuanensis, which is consistent with previous phylogenetic analysis based on morphological characteristics, but contrasts with other studies using multiple gene fragments. Moreover, although the duplication of trnM occurred in all seven Oreolalax species, the translocation of trnQ and trnM occurred differently in O. omeimontis to the other six, and this unique rearrangement would happen after the speciation of O. omeimontis. In general, this study sheds new light on the phylogenetic relationships and gene rearrangements of Archaeobatrachia.

The revised complete mitogenome sequence of the tree frog Polypedatesmegacephalus (Anura, Rhacophoridae) by next-generation sequencing and phylogenetic analysis.

The mitochondrial genome (mitogenome) sequence of the tree frog Polypedates megacephalus (16,473 bp) was previously reported as having the unusual characteristic of lacking the ND5 gene. In this study, a new mitogenome of P. megacephalus (19,952 bp) was resequenced using the next-generation sequencing (NGS) and standard Sanger sequencing technologies. It was discovered that the ND5 gene was not lost but translocated to the control region (CR) from its canonical location between the ND4 and ND6 genes. In addition, a duplicated control region was found in the new mitogenome of this species. Conservative region identification of the ND5 gene and phylogenetic analysis confirmed that the ND5 gene was located between two control regions. The phylogenetic relationship among 20 related species of anura revealed a rearrangement of the ND5 gene during the evolutionary process. These results also highlighted the advantages of next-generation sequencing. It will not only decrease the time and cost of sequencing, but also will eliminate the errors in published mitogenome databases.

The Complete Mitochondrial Genome of Platysternon megacephalum peguense and Molecular Phylogenetic Analysis.

Platysternon megacephalum is the only living representative species of Platysternidae and only three subspecies remain: P. m. megalorcephalum, P. m. shiui, and P. m. peguense. However, previous reports implied that P. m. peguense has distinct morphological and molecular features. The characterization of the mitogenome has been accepted as an efficient means of phylogenetic and evolutionary analysis. Hence, this study first determined the complete mitogenome of P. m. peguense with the aim to identify the structure and variability of the P. m. peguense mitogenome through comparative analysis. Furthermore, the phylogenetic relationship of the three subspecies was tested. Based on different tRNA gene loss and degeneration of these three subspecies, their rearrangement pathways have been inferred. Phylogenetic analysis showed that P. m. peguense is a sister group to (P. m. megalorcephalum and P. m. shiui). Furthermore, the divergence time estimation of these three subspecies coincided with the uplift of the Tibetan Plateau. This study shows that the genetic distances between P. m. peguense and the other two subspecies are comparable to interspecific genetic distances, for example within Mauremys. In general, this study provides new and meaningful insights into the evolution of the three Platysternidae subspecies.

The complete mitogenome of the splendid japalure Japalura splendida (Squamata, Agamidae).

The complete mitogenome of Japalura splendida (16,673 bp in length) is determined and analyzed in this study. It contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and one non-coding regions. All the genes in J. splendida are distributed on the H-strand, except for the ND6 gene and seven tRNA genes which are encoded on the L-strand. The phylogenetic tree suggests that J. splendida and Japalura flaviceps formed a sister group and reveals the order ((((Acanthosaura lepidogaster, Acanthosaura armata), ((J. splendida, J. flaviceps), Pseudocalotes microlepis))), Calotes versicolor) with substantial support for the monophyly.

The complete mitogenome of the granular torrent frog, Amolops granulosus (Anura: Ranidae).

We obtained the complete mitochondrial genome of Amolops granulosus, which was 17,785 bp in length and it contained the 37 typical mitochondrial genes: 2 ribosomal RNAs, 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and 1 control region (CR). The hotspot of gene arrangement was ranged as 'W-gap-OL-gap-A-N-gap-C-Y' which consisted with most published Amolops mitogenomes. Our phylogenetic results suggested the gene arrangement of 'WANCY' region can facilitate to distinguish the Amolops species as an efficient genetic marker.

Metagenomic Study Suggests That the Gut Microbiota of the Giant Panda (Ailuropoda melanoleuca) May Not Be Specialized for Fiber Fermentation.

Bamboo-eating giant panda (Ailuropoda melanoleuca) is an enigmatic species, which possesses a carnivore-like short and simple gastrointestinal tract (GIT). Despite the remarkable studies on giant panda, its diet adaptability status continues to be a matter of debate. To resolve this puzzle, we investigated the functional potential of the giant panda gut microbiome using shotgun metagenomic sequencing of fecal samples. We also compared our data with similar data from other animal species representing herbivores, carnivores, and omnivores from current and earlier studies. We found that the giant panda hosts a bear-like gut microbiota distinct from those of herbivores indicated by the metabolic potential of the microbiome in the gut of giant pandas and other mammals. Furthermore, the relative abundance of genes involved in cellulose- and hemicellulose-digestion, and enrichment of enzymes associated with pathways of amino acid degradation and biosynthetic reactions in giant pandas echoed a carnivore-like microbiome. Most significantly, the enzyme assay of the giant panda's feces indicated the lowest cellulase and xylanase activity among major herbivores, shown by an in-vitro experimental assay of enzyme activity for cellulose and hemicellulose-degradation. All of our results consistently indicate that the giant panda is not specialized to digest cellulose and hemicellulose from its bamboo diet, making the giant panda a good mammalian model to study the unusual link between the gut microbiome and diet. The increased food intake of the giant pandas might be a strategy to compensate for the gut microbiome functions, highlighting a strong need of conservation of the native bamboo forest both in high- and low-altitude ranges to meet the great demand of bamboo diet of giant pandas.