Biology subjects

Aitken, S.

Publications and source records attributed to Aitken, S..

3 recordsLinked to original sources

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

Modular environmental pleiotropy of genes involved in local adaptation to climate despite physical linkage

BackgroundPhysical linkage among genes shaped by different sources of selection is a fundamental aspect of genetic architecture. Theory predicts that evolution in complex environments selects for modular genetic architectures and high recombination rates among loci shaped by different sources of selection. However, limited data exist to test these predictions because the field lacks consensus for how to control for intercorrelated environmental variables. Here, we introduce a co-association network analysis, which clusters loci based on differing environmental associations, and use it to study the genetic architecture of local adaptation to climate in lodgepole pine (Pinus contorta).\n\nResultsWe identified many modules of genes associated with distinct environments (aridity, freezing, geography), and discovered low recombination rates among some candidate genes in different modules. We observed limited evidence for environmental pleiotropic effects on distinct aspects of climate. We also found limited correspondence between the modularity of co-association networks and gene regulatory networks. We compared co-association networks to associations with principal components, and found the latter can lead to misinterpretation. Finally, we used simulations to illustrate the benefits and caveats of co-association networks.\n\nConclusionsCo-association networks provided a useful framework for studying modularity. Our results supported the prediction that evolution to complex environments selects for modular genetic architectures, but some of our results went against the prediction that selection would increase recombination among loci experiencing different sources of selection. These results give new insight into evolutionary debates about the extent of modularity and pleiotropy in the evolution of genetic architectures.

evolutionary biology↗

bioRxiv2017

The circadian dynamics of small nucleolar RNA

The circadian regulation of gene expression allows plants and animals to anticipate predictable environmental changes. While the influence of the circadian clock has recently been shown to extend to ribosome biogenesis, the dynamics and regulation of the many small nucleolar RNA that are required in pre-ribosomal RNA folding and modification are unknown. Using a novel computational method, we show that 18S and 28S pre-rRNA are subject to circadian regulation in a nuclear RNA sequencing time course. A population of snoRNA with circadian expression is identified that is functionally associated with rRNA modification. More generally, we find the abundance of snoRNA known to modify 18S and 28S to be inversely correlated with the abundance of their target. Cyclic patterns in the expression of a number of snoRNA indicate a coordination with rRNA maturation, potentially through an upregulation in their biogenesis, or their release from mature rRNA at the end of the previous cycle of rRNA maturation, in antiphase with the diurnal peak in pre-rRNA. Few cyclic snoRNA have cyclic host genes, indicating the action of regulatory mechanisms in addition to transcriptional activation of the host gene. For highly-expressed independently transcribed snoRNA, we find a characteristic RNA polymerase II and H3K4me3 signature that correlates with mean snoRNA expression over the day.

bioinformatics↗