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Biology subjects

Hirschberg, I.

Publications and source records attributed to Hirschberg, I..

2 recordsLinked to original sources

Standing genetic variation fuels rapid evolution of herbicide resistance in blackgrass

Repeated herbicide applications exert enormous selection on blackgrass (Alopecurus myosuroides), a major weed in cereal crops of the temperate climate zone including Europe. This inadvertent large-scale experiment gives us the opportunity to look into the underlying genetic mechanisms and evolutionary processes of rapid adaptation, which can occur both through mutations in the direct targets of herbicides and through changes in other, often metabolic, pathways, known as non-target-site resistance. How much either type of adaptation relies on de novo mutations versus pre-existing standing variation is important for developing strategies to manage herbicide resistance. We generated a chromosome-level reference genome for A. myosuroides for population genomic studies of herbicide resistance and genome-wide diversity across Europe in this species. Bulked-segregant analysis evidenced that non-target-site resistance has a complex genetic architecture. Through empirical data and simulations, we showed that, despite its simple genetics, target-site resistance mainly results from standing genetic variation, with only a minor role for de novo mutations.

evolutionary biology↗

DAP5 enables translation re-initiation on structured messenger RNAs

Half of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is selectively required for re-initiation at the main CDS following uORF translation. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-mediated re-initiation occurs on messenger RNAs (mRNAs) with long, structure-prone 5' leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates re-initiation by unrecycled post-termination 40S subunits. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors.

molecular biology↗