Zaytseva, O. | bioRxiv Science

bioRxiv2020

Transcriptional repression of Myc underlies AGO1's tumour suppressor function

Here we report novel tumour suppressor activity for the Drosophila Argonaute family RNA binding protein AGO1, a component of the miRNA-dependent RNA-induced silencing complex (RISC). The mechanism for growth inhibition does not, however, involve canonical roles as part of the RISC; rather AGO1 controls cell and tissue growth by functioning as a direct transcriptional repressor of the master regulator of growth, Myc. AGO1 depletion in wing imaginal discs drives a significant increase in ribosome biogenesis, nucleolar expansion, and cell growth in a manner dependent on Myc abundance. Moreover, increased Myc promoter activity and elevated Myc mRNA in AGO1 depleted animals requires RNA Pol II transcription. Further support for transcriptional AGO1 functions is provided by physical interaction with the RNA Pol II transcriptional machinery (chromatin remodelling factors and Mediator Complex), punctate nuclear localisation in euchromatic regions and overlap with Polycomb Group transcriptional silencing loci. Moreover, significant AGO1 enrichment is observed on the Myc promoter and AGO1 interacts with the Myc transcriptional activator Psi. Together our data show AGO1 functions outside of the RISC to repress Myc transcription and inhibit developmental cell and tissue growth.

developmental biology↗

bioRxiv2017

Coat color allele and mtDNA haplotype distributions in Russian cat populations: a citizen-science research

This work has started as a project for the summer school in molecular and theoretical biology. Efficient teaching and learning modern methods of molecular biology and population genetics in a two-week study course for high school students needs an attractive subject. We chose phylogeography of the domestic cat as the subject of our project because 1) everybody likes cats; 2) cats are polymorphic for several coat color mutations, which can be easily detected by street survey or in the photographs; 3) samples for DNA extraction are easy to collect without posing ethical and biosafety problems; 4) rich background information of geographical distribution of coat color alleles and variation in mtDNA is available; 5) phylogeography of cat population in Russia is poorly studied and therefore new data collected in this large territory may shed a light on the global cat distribution and on the origin of the fancy breeds.\n\nDuring the project students studied coat color and mitotype distribution across Russian random bred cats. The basics of field (observations of natural cat populations, hair collection), formal (inheritance of coat colors), mathematical population (allele frequency distributions and their comparisons, building phylogenetic trees, multidimensional scaling), and molecular (DNA extraction and amplification, quality control of DNA sequencing data) genetics were covered.\n\nWe scored coat color phenotypes in 1182 cats and sequenced mtDNA control region from hair samples of 38 cats from 18 geographical sites. Analysis of coat color alleles frequencies and mitotype distribution confirmed relative homogeneity of gene pools of Russian cat populations, indicating their recent origin. We found several unique mitotypes and demonstrated that OL1 mitotype, previously found only in Siberian fancy breed, was present in random bred cats from several Russian cities. This contributes to the discussion on the origin of the Siberian breed of cats, and supports the view that Siberians is a recent breed created in the 1980s by breeding of selected representatives of the random bred population.

genetics↗