Chromosome-level assemblies of multiple Arabidopsis genomes reveal hotspots of rearrangements with altered evolutionary dynamics

Despite hundreds of sequenced Arabidopsis genomes, very little is known about the degree of genomic collinearity within single species, due to the low number of chromosome-level assemblies. Here, we report chromosome-level reference-quality assemblies of seven Arabidopsis thaliana accessions selected across its global range. Each genome reveals between 13-17Mb rearranged, and 5-6Mb non-reference sequences introducing copy-number changes in similar to 5000 genes, including similar to 1900 non-reference genes. Quantifying the collinearity between the genomes reveals similar to 350 euchromatic regions, where accession-specific tandem duplications destroy the collinearity between the genomes. These hotspots of rearrangements are characterized by reduced meiotic recombination in hybrids and genes implicated in biotic stress response. This suggests that hotspots of rearrangements undergo altered evolutionary dynamics, as compared to the rest of the genome, which are mostly based on the accumulation of new mutations and not on the recombination of existing variation, and thereby enable a quick response to the biotic stress. Despite tremendous genomic resources in the Arabidopsis community, only a few whole genome de novo assemblies are available. Here, the authors report chromosome-level reference-quality assemblies of seven A. thaliana accessions and reveal hotspots of rearrangements with altered evolutionary dynamics

MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia

Progranulin deficiency is thought to cause some forms of frontotemporal dementia (FTD), a major early-onset age-dependent neurodegenerative disease. How progranulin (PGRN) expression is regulated is largely unknown. We identified an evolutionarily conserved binding site for microRNA-29b (miR-29b) in the 3\u27 untranslated region (3\u27UTR) of the human PGRN (hPGRN) mRNA. miR-29b downregulates the expression of luciferase through hPGRN or mouse PGRN (mPGRN) 3\u27UTRs, and the regulation was abolished by mutations in the miR-29b binding site. To examine the direct effect of manipulating endogenous miR-29b on hPGRN expression, we established a stable NIH3T3 cell line that expresses hPGRN under the control of the cytomegalovirus promoter. Ectopic expression of miR-29b decreased hPGRN expression at the both mRNA and protein levels. Conversely, knockdown of endogenous miR-29b with locked nucleic acid increased the production and secretion of hPGRN in NIH3T3 cells. Endogenous hPGRN in HEK 293 cells was also regulated by miR-29b. These findings identify miR-29b as a novel posttranscriptional regulator of PGRN expression, raising the possibility that miR-29b or other miRNAs might be targeted therapeutically to increase hPGRN levels in some FTD patients