mRNA nuclear export: how mRNA identity features distinguish functional RNAs from junk transcripts.

The division of the cellular space into nucleoplasm and cytoplasm promotes quality control mechanisms that prevent misprocessed mRNAs and junk RNAs from gaining access to the translational machinery. Here, we explore how properly processed mRNAs are distinguished from both misprocessed mRNAs and junk RNAs by the presence or absence of various 'identity features'.

GC-content biases in protein-coding genes act as an "mRNA identity" feature for nuclear export.

It has long been observed that human protein-coding genes have a particular distribution of GC-content: the 5' end of these genes has high GC-content while the 3' end has low GC-content. In 2012, it was proposed that this pattern of GC-content could act as an mRNA identity feature that would lead to it being better recognized by the cellular machinery to promote its nuclear export. In contrast, junk RNA, which largely lacks this feature, would be retained in the nucleus and targeted for decay. Now two recent papers have provided evidence that GC-content does promote the nuclear export of many mRNAs in human cells.

The GC-content at the 5' ends of human protein-coding genes is undergoing mutational decay.

BACKGROUND: In vertebrates, most protein-coding genes have a peak of GC-content near their 5' transcriptional start site (TSS). This feature promotes both the efficient nuclear export and translation of mRNAs. Despite the importance of GC-content for RNA metabolism, its general features, origin, and maintenance remain mysterious. We investigate the evolutionary forces shaping GC-content at the transcriptional start site (TSS) of genes through both comparative genomic analysis of nucleotide substitution rates between different species and by examining human de novo mutations. RESULTS: Our data suggests that GC-peaks at TSSs were present in the last common ancestor of amniotes, and likely that of vertebrates. We observe that in apes and rodents, where recombination is directed away from TSSs by PRDM9, GC-content at the 5' end of protein-coding gene is currently undergoing mutational decay. In canids, which lack PRDM9 and perform recombination at TSSs, GC-content at the 5' end of protein-coding is increasing. We show that these patterns extend into the 5' end of the open reading frame, thus impacting synonymous codon position choices. CONCLUSIONS: Our results indicate that the dynamics of this GC-peak in amniotes is largely shaped by historic patterns of recombination. Since decay of GC-content towards the mutation rate equilibrium is the default state for non-functional DNA, the observed decrease in GC-content at TSSs in apes and rodents indicates that the GC-peak is not being maintained by selection on most protein-coding genes in those species.

Methanobrevibacter attenuation via probiotic intervention reduces flatulence in adult human: A non-randomised paired-design clinical trial of efficacy.

TRIAL DESIGN: The aim of this study was to investigate which of the gut microbes respond to probiotic intervention, as well as study whether they are associated with gastrointestinal symptoms in a healthy adult human. For the experimental purpose, twenty-one healthy adults were recruited and received probiotic mixture, which is composed of five Lactobacilli strains and two Bifidobacteria strains, once a day for 60 days. Defecation survey and Bioelectrical Impedance Analysis were conducted pre- and post-administration to measure phenotypic differences. Stool samples of the subjects were collected twice. METHODS: The statistical analysis was performed for pair designed metagenome data with 11 phenotypic records of the bioelectrical impedance body composition analyzer and 6 responses of the questionnaires about gastrointestinal symptom. Furthemore, correlation-based network analysis was conducted for exploring complex relationships among microbiome communities. RESULTS: The abundances of Citrobacter, Klebsiella, and Methanobrevibacter were significantly reduced, which are strong candidates to be highly affected by the probiotic administration. In addition, interaction effects were observed between flatulence symptom attenuation and decreasing patterns of the Methanobrevibacter abundance. CONCLUSIONS: These results reveal that probiotic intervention modulated the composition of gut microbiota and reduced the abundance of potential pathogens (i.e. Citrobacter and Klebsiella). In addition, methanogens (i.e. Methanobrevibacter) associated with the gastrointestinal symptom in an adult human.

Gut microbiota Modulated by Probiotics and Garcinia cambogia Extract Correlate with Weight Gain and Adipocyte Sizes in High Fat-Fed Mice.

Results of recent studies on gut microbiota have suggested that obesogenic bacteria exacerbate obesity and metabolic dysfunction in the host when fed a high fat diet (HFD). In order to explore obesity-associated bacterial candidates and their response to diet, the composition of faecal bacterial communities was investigated by analyzing 16S rRNA gene sequences in mice. Dietary intervention with probiotics and Garcinia cambogia extract attenuated weight gain and adipocyte size in HFD-fed mice. To identify obesity-causative microbiota, two statistical analyses were performed. Forty-eight bacterial species were found to overlap between the two analyses, indicating the commonly identified species as diet-driven and obesity-associated, which would make them strong candidates for host-microbiome interaction on obesity. Finally, correlation based network analysis between diet, microbe, and host revealed that Clostridium aminophilum, a hyper-ammonia-producing bacterium, was highly correlated with obesity phenotypes and other associated bacteria, and shown to be suppressed by the combination of probiotics and Garcinia cambogia extract. Results of the present study suggest that probiotics and Garcinia cambogia extract alleviate weight gain and adiposity, in part via differentially modulating the composition of gut microbiota in HFD fed mice.