Biology subjects

Hahn, Y.

Publications and source records attributed to Hahn, Y..

3 recordsLinked to original sources

bioRxiv2021

Meiosis-Specific Cohesin Complexes Display Distinct and Essential Roles in Mitotic ESC Chromosomes

Cohesin is a chromosome-associated SMC-kleisin complex that mediates sister chromatid cohesion, recombination, and most chromosomal processes during mitosis and meiosis. Through high-resolution 3D-structured illumination microscopy and functional analyses, we report multiple biological processes associated with the meiosis-specific cohesin components, REC8 and STAG3, and the distinct loss of function of meiotic cohesin during the cell cycle of embryonic stem cells (ESCs). First, we show that REC8 is translocated into the nucleus in a STAG3-dependent manner. REC8/STAG3-containing cohesin regulates chromosome topological properties and specifically maintains centromeric cohesion. Second, REC8 and mitotic cohesin RAD21 are located at adjacent sites but predominantly at nonoverlapping sites on ESC chromosomes, implying that REC8 can function independent of RAD21 in ESCs. Third, knockdown of REC8-cohesin not only leads to higher rates of premature centromere separation and stalled replication forks, which can cause proliferation and developmental defects, but also enhances compaction of the chromosome structure by hyperloading of retinoblastoma protein-condensin complexes from prophase onward. We propose that the delicate balance between mitotic and meiotic cohesins may regulate ESC- specific chromosomal organization and mitotic program.

molecular biology↗

bioRxiv2020

An alternative miRISC targeting a coding mutation site in FOXL2 links to granulosa cell tumor

Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult-type granulosa cell tumors (AGCTs), introduces a target site for miR-1236, which induces haploinsufficiency of the tumor-suppressor FOXL2. This miR-1236-mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA-loaded RNA-induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and mouse model of AGCT, the inversely regulated variant FOXL2 abundance with the miR-1236 levels was highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation-mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA-targeting disease-associated mutations in the CDS by forming a non-canonical miRISC.

cancer biology↗

bioRxiv2016

The effects of increasing the number of taxa on inferences of molecular convergence

Convergent evolution provides insight into the link between phenotype and genotype. Recently, large-scale comparative studies of convergent evolution have become possible, but researchers are still trying to determine the best way to design these types of analyses. One aspect of molecular convergence studies that has not yet been investigated is how taxonomic sample size affects inferences of molecular convergence. Here we show that increased sample size decreases the amount of inferred molecular convergence associated with the three convergent transitions to a marine environment in mammals. The sampling of more taxa--both with and without the convergent phenotype--reveals that alleles associated only with marine mammals in small datasets are actually more widespread, or are not shared by all marine species. The sampling of more taxa also allows finer resolution of ancestral substitutions, revealing that they are not in fact on lineages leading to solely marine species. We revisit a previous study on marine mammals and find that only 7 of the reported 43 genes with convergent substitutions still show signs of convergence with a larger number of background species. However, 4 of those 7 genes also showed signs of positive selection in the original analysis and may still be good candidates for adaptive convergence. Though our study is framed around the convergence of marine mammals, we expect our conclusions on taxonomic sampling are generalizable to any study of molecular convergence.

genomics↗