Comparative Component Analysis of Exons with Different Splicing Frequencies

Transcriptional isoforms are not just random combinations of exons. What has caused exons to be differentially spliced and whether exons with different splicing frequencies are subjected to divergent regulation by potential elements or splicing signals? Beyond the conventional classification for alternatively spliced exons (ASEs) and constitutively spliced exons (CSEs), we have classified exons from alternatively spliced human genes and their mouse orthologs (12,314 and 5,464, respectively) into four types based on their splicing frequencies. Analysis has indicated that different groups of exons presented divergent compositional and regulatory properties. Interestingly, with the decrease of splicing frequency, exons tend to have greater lengths, higher GC content, and contain more splicing elements and repetitive elements, which seem to imply that the splicing frequency is influenced by such factors. Comparison of non-alternatively spliced (NAS) mouse genes with alternatively spliced human orthologs also suggested that exons with lower splicing frequencies may be newly evolved ones which gained functions with splicing frequencies altered through the evolution. Our findings have revealed for the first time that certain factors may have critical influence on the splicing frequency, suggesting that exons with lower splicing frequencies may originate from old repetitive sequences, with splicing sites altered by mutation, gaining novel functions and become more frequently spliced

Involvement of AmphiREL, a Rel-like gene identified in Brachiastoma belcheri, in LPS-induced response: Implication for evolution of Rel subfamily genes

AbstractRel/NF-κB family genes are important transcriptional factors regulating vital activities of immunity response, but no Rel/NF-κB gene has been identified in amphioxus. In this study, we have not only identified and characterized a Rel-like gene from Brachiastoma belcheri, but also extensively studied the evolution of Rel gene subfamily. We found that: 1) the amphioxus genome contains an AmphiREL gene encoding a Rel/NF-κB homolog, and AmphiREL gene was involved in the innate immune response of LPS stimulation in amphioxus. 2) Gene synteny comparison and structure comparison suggested that AmphiREL is an orthologous gene of human RELB, and is a paralogous gene of human RELA and REL. 3) Structural changes of Rel subfamily proteins are diverse during the evolution process, and imply their functional diversity. 4) The Rel subfamily genes have undergone very strong purifying selection. Together, our results provide important clues for understanding the evolution and function of Rel subfamily genes

Innovation Dynamics of Cultural Production: Evidence in Rap Lyrics

Culture is a driving force in organizing the structure of societies, and is conjoined with economic development. However, quantifying the impact of culture is difficult. Culture manifests itself in cultural production, through art, performance, music, etc. Innovation and influence in cultural production industries partially determines product quality. Using techniques from the “digitized humanities”, we agnostically identify informational distance to describe the spatiotemporal dynamics of innovation and influence in Rap music lyrics. Rap emphasizes lyricism and hometown pride more than other genres of popular music, and is interesting as a globally impactful manifestation of the racially segregated labor market in the U.S. Resources and production are not spread evenly within an economy. Geographic clustering of economic activity is well discussed across the social sciences. Although first discussed in relation to manufacturing, urban agglomeration has been observed empirically for both cultural production and innovation in general. We find that number of Rappers and maximum novelty scale with overall and Black/African-American population at the MSA-level, suggesting an increasing return to maximum novelty through greater chance of recombination. Rapper population is predicted by Black/African-American population, while measures of song quality are predicted by total population. This paper contributes a novel dataset and application of the methodology to economic questions of cultural production

Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures

The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, emphasized the urgent need for development of novel antivirals. Small-molecule chemical probes offer both to reveal aspects of virus replication and to serve as leads for antiviral therapeutic development. Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5′-end. Nuclear magnetic resonance–based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA structures within the 5′ untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA–targeted antivirals