When considering the control of gene expression, the focus has traditionally been on transcriptional regulation. Recently, however, the large contribution made by mRNA decay has become difficult to ignore. Large-scale analyses indicate that as many as half of all changes in the amounts of mRNA in some responses can be attributed to altered rates of decay. In this article, we discuss some of the mechanisms that are used by the cell to mediate and regulate this intriguing process.

Summary The mechanisms utilized by viruses to protect their transcripts from the cellular RNA decay machinery, as well as the biological relevance of this protection, are largely unknown. We demonstrate that Sindbis virus uses U-rich 3’ UTR sequences in its RNAs to recruit the cellular HuR protein during infections of both human and mosquito cells. HuR binds viral RNAs with high specificity and affinity. Furthermore, Sindbis virus induces the selective movement of HuR protein out of the nucleus of mammalian cells during infection thereby increasing the cytoplasmic pool of the protein available to the virus. Finally, knockdown of HuR results in a significant increase in the rate of decay of Sindbis virus RNAs and diminishes viral yields in both human and mosquito cells. Collectively these data indicate that Sindbis virus, and likely other alphaviruses, usurp the HuR protein to avoid the cellular mRNA decay machinery and maintain a highly productive infection.

Different patterns of sweet liking exist. For some, liking increases as concentration increases up to a point at which it typically plateaus. These individuals are referred to as sweet likers. How sweet likers’ beverage intake, especially sugar sweetened beverage intake, differs from sweet dislikers’ beverage intake is not well characterized. A total of 953 visitors (650 adults; 62.0% women; 303 children; 58.7% girls) to the Denver Museum of Nature & Science rated the taste intensity and liking of 5 sucrose solutions that spanned concentrations typically encountered in sugar-sweetened beverages (0.0–13.7% w/v) using visual analog scales. Beverage intake by adults was quantified using the validated BEVQ-15 questionnaire. Among adults, hierarchical cluster analysis identified three clusters of liking patterns (likers, dislikers, and neutrals). Among children, two clusters of liking patterns were identified (likers and dislikers). For both adults and children, BMI, percent body fat, age, and sex did not differ between clusters. Concentration by cluster interaction effects were observed for both adults and children. Adult sweet likers consumed more energy from all beverages, more sweetened juice and tea, and less water than those in other clusters. Sweet liker status may be a useful predictor of increased energy intake from beverages, but prospective trials are necessary to confirm this utility.

Genetics of taste Lab citizen Scientists † oral microbiome dysbiosis has been associated with various local and systemic human diseases such as dental caries, periodontal disease, obesity, and cardiovascular disease. Bacterial composition may be affected by age, oral health, diet, and geography, although information about the natural variation found in the general public is still lacking. in this study, citizen-scientists used a crowdsourcing model to obtain oral bacterial composition data from guests at the Denver Museum of nature & Science to determine if previously suspected oral microbiome associations with an individual's demographics, lifestyle, and/or genetics are robust and generalizable enough to be detected within a general population. consistent with past research, we found bacterial composition to be more diverse in youth microbiomes when compared to adults. Adult oral microbiomes were predominantly impacted by oral health habits, while youth microbiomes were impacted by biological sex and weight status. the oral pathogen Treponema was detected more commonly in adults without recent dentist visits and in obese youth. Additionally, oral microbiomes from participants of the same family were more similar to each other than to oral microbiomes from non-related individuals. these results suggest that previously reported oral microbiome associations are observable in a human population containing the natural variation commonly found in the general public. furthermore, these results support the use of crowdsourced data as a valid methodology to obtain community-based microbiome data. Oral microbiome dysbiosis has been associated with various local and systemic human diseases including dental caries, periodontal disease, obesity, and cardiovascular disease 1-5. Proper oral health care habits can help reduce abundance of taxa associated with pathogenic states. For example, flossing has been associated with decreased concentrations of the dental pathogen Streptococcus mutans 6 , and brushing of the teeth and tongue significantly decreases microbes associated with dental diseases 7,8. It is estimated that over 600 bacteria species are commonly associated with the oral microbiome, with a subset of these proposed to be part of a consortium called the "core oral microbiome" 9-11. Genera often considered associated with the core microbiome include Streptococcus, Veillonella, Neisseria, and Actinomyces, which are shared by most healthy individuals 12,13. Maintaining the balance of core healthy bacteria in the oral microbiota plays a critical role not only in oral health but in overall health. Oral microbiome composition is suspected to be affected by additional variables including host genetics 14,15 , geography 4,16 , diet 17,18 , age 19-21 , and cohabitation 22-24. For example, comparative studies between European, African, Asian, and American populations discovered microbial variation between populations, and other studies describe ethnicity-specific clustering within the United States 15,25,26. The effect of diet...

The positive-sense transcripts of Sindbis virus (SINV) resemble cellular mRNAs in that they possess a 5 cap and a 3 poly(A) tail. It is likely, therefore, that SINV RNAs must successfully overcome the cytoplasmic mRNA decay machinery of the cell in order to establish an efficient, productive infection. In this study, we have taken advantage of a temperature-sensitive polymerase to shut off viral transcription, and we demonstrate that SINV RNAs are subject to decay during a viral infection in both C6/36 (Aedes albopictus) and baby hamster kidney cells. Interestingly, in contrast to most cellular mRNAs, the decay of SINV RNAs was not initiated by poly(A) tail shortening in either cell line except when most of the 3 untranslated region (UTR) was deleted from the virus. This block in deadenylation of viral transcripts was recapitulated in vitro using C6/36 mosquito cell cytoplasmic extracts. Two distinct regions of the 319-base SINV 3 UTR, the repeat sequence elements and a U-rich domain, were shown to be responsible for mediating the repression of deadenylation of viral mRNAs. Through competition studies performed in parallel with UV cross-linking and functional assays, mosquito cell factors-including a 38-kDa protein-were implicated in the repression of deadenylation mediated by the SINV 3 UTR. This same 38-kDa protein was also implicated in mediating the repression of deadenylation by the 3 UTR of another alphavirus, Venezuelan equine encephalitis virus. In summary, these data provide clear evidence that SINV transcripts do indeed interface with the cellular mRNA decay machinery during an infection and that the virus has evolved a way to avoid the major deadenylation-dependent pathway of mRNA decay.The Alphavirus genus of the Togaviridae family consists primarily of a group of viruses with single-stranded, positive-sense RNA genomes that are transmitted by arthropods and replicate exclusively within the cytoplasm of infected cells (45, 51). Sindbis virus (SINV), the prototypic virus of the genus, encodes genomic and subgenomic RNAs that are capped on the 5Ј terminus, polyadenylated at the 3Ј end, and contain 5Ј and 3Ј untranslated regions (UTRs) similar to cellular mRNAs. The viral genomic RNA, in fact, functions as an mRNA immediately upon infection. This strategy of mimicking cellular mRNAs has potential advantages and disadvantages for the virus. While this strategy allows viral RNAs to be effectively translated, viral transcripts may also be fully subject to the activity of the mRNA decay machinery within the cytoplasm of the host cell. Aspects of this anticipated interplay between SINV transcripts and cellular mRNA decay enzymes were investigated in this study.