Biology subjects

Hirano, T.

Publications and source records attributed to Hirano, T..

22 records · Page 2Linked to original sources

bioRxiv2020

NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells

During murine germ cell development, male germ cells enter the mitotically arrested G0 stage, which is an initial step of sexually dimorphic differentiation. The male specific RNA-binding protein NANOS2 has a key role in suppressing the cell cycle in germ cells. However, the detailed mechanism of how NANOS2 regulates the cell cycle remains unclear. Using single-cell RNA sequencing (scRNA-seq), we extracted the cell cycle state of each germ cell in wild-type and Nanos2-KO testes, and revealed that Nanos2 expression starts in mitotic cells and induces mitotic arrest. We also found that NANOS2 and p38 MAPK work in parallel to regulate the cell cycle, suggesting that several different cascades are involved in the induction of cell cycle arrest. Furthermore, we identified Rheb, a regulator of mTORC1, and Ptma as possible targets of NANOS2. We propose that the repression of the cell cycle is a primary function of NANOS2 and that it is mediated via the suppression of mTORC1 activity by repressing Rheb in a post-transcriptional manner.

developmental biology↗

bioRxiv2019

Genetic factor for twisting legume pods identified by fine-mapping of shattering-related traits in azuki bean and yard-long bean

Legumes have evolved a unique manner of seed dispersal in that the seed pods explosively split open with helical tension generated by sclerenchyma on the endocarp. During domestication, azuki bean (Vigna angularis) and yard-long bean (Vigna unguiculata cv-gr. Sesquipedalis) have reduced or lost the sclerenchyma and lost the shattering behavior of seed pods. Here we performed fine-mapping with back-crossed populations and narrowed the candidate genomic region down to 4 kbp in azuki bean and 13 kbp in yard-long bean. Among genes located in these regions, we found MYB26 genes encoded truncated proteins in both the domesticated species. We also found in azuki bean and other legumes that MYB26 is duplicated and only the duplicated copy is expressed in seed pods. Interestingly, in Arabidopsis MYB26 is single copy and is specifically expressed in anther to initiate secondary wall thickening that is required for anther dehiscence. These facts indicated that, in legumes, MYB26 has been duplicated and acquired a new role in development of pod sclerenchyma. However, pod shattering is unfavorable phenotype for harvesting and thus has been selected against by human.

genetics↗

bioRxiv2018

Structural basis of HEAT-kleisin interactions in the human condensin I subcomplex

ABSTRUCTCondensin I is a multi-protein complex that plays an essential role in mitotic chromosome assembly and segregation in eukaryotes. It is composed of five subunits: two SMC (SMC2 and SMC4), a kleisin (CAP-H) and two HEAT-repeat (CAP-D2 and -G) subunits. Although it has been shown that balancing acts of the two HEAT-repeat subunits enable this complex to support dynamic assembly of chromosomal axes in vertebrate cells, its underlying mechanisms remain poorly understood. Here, we report the crystal structure of a human condensin I subcomplex comprising hCAP-G and hCAP-H. hCAP-H binds to the concave surfaces of a harp-shaped HEAT repeat domain of hCAP-G. A physical interaction between hCAP-G and hCAP-H is indeed essential for mitotic chromosome assembly recapitulated in Xenopus egg cell-free extracts. Furthermore, this study reveals that the human CAP-G-H subcomplex has the ability to interact with not only a double-stranded DNA, but also a single-stranded DNA, implicating potential, functional divergence of the vertebrate condensin I complex in mitotic chromosome assembly.

cell biology↗

bioRxiv2017

Ki-67 and condensins support the integrity of mitotic chromosomes through distinct mechanisms

Although condensins play essential roles in mitotic chromosome assembly, Ki-67, a protein localizing to the periphery of mitotic chromosomes, had also been shown to make a contribution to the process. To examine their respective roles, we generated a set of HCT116-based cell lines expressing Ki-67 and/or condensin subunits that were fused with an auxin-inducible degron for their conditional degradation. Both the localization and the dynamic behavior of Ki-67 on mitotic chromosomes were not largely affected upon depletion of condensin subunits, and vice versa. When both Ki-67 and SMC2 (a core subunit of condensins) were depleted, ball-like chromosome clusters with no sign of discernible thread-like structures were observed. This severe defective phenotype was distinct from that observed in cells depleted of either Ki-67 or SMC2 alone. Our results show that Ki-67 and condensins, which localize to the external surface and the central axis of mitotic chromosomes, respectively, have independent yet cooperative functions in supporting the structural integrity of mitotic chromosomes.\n\nList of Abbreviations used

cell biology↗