Wilson, A. R. | bioRxiv Science

bioRxiv2018

Slow transcriptional elongation causes embryonic lethality and perturbs kinetic coupling of long neural genes

Alternative splicing (AS) is a highly regulated process that increases protein diversity and is critical for cell differentiation and development. The rate of RNA Polymerase II (RNAPII) elongation has an important role in the control of AS. We generated mouse embryonic stem cells (ESCs) knocked-in for a slow elongating form of RNAPII and show that a reduced transcriptional elongation rate causes early embryonic lethality in mice and impairs the differentiation of ESCs into the neural lineage. The reduced elongation rate caused changes in splicing and in gene expression in ESCs and along the pathway of neuronal differentiation. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is more predominant in ESC-differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development.

molecular biology↗

bioRxiv2017

Human activities influence the direction and magnitude of local biodiversity change over time

In recent decades, environmental drivers of community change have been associated with changes in biodiversity from local to global scales. Here we evaluate the role of anthropogenic drivers in marine ecosystems as drivers of change in local species richness with a meta-analysis of a novel dataset of temporal change in species richness. We paired biodiversity data from 144 sites with large-scale drivers derived from geospatial databases: human cumulative impact scores, sea surface temperature change, nutrient loading, and invasion potential. Three specific drivers (nutrient inputs, rate of linear temperature change, and non-native species invasion potential) explained patterns in local marine species richness change. We show that these drivers have opposing effects on biodiversity trends. In some cases, variability in drivers can create contrasting directions of change yielding observations of no net change when localities are pooled in an attempt to find a global average. Further, long-term studies reveal different effects of drivers that are not observed in short-term studies. These findings begin to explain high variability observed in species diversity trends at local scales. Formally attributing local species diversity change to human drivers is essential to understanding global patterns of local species diversity change and their consequences.

ecology↗