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Publication : Nuclear translocation of MTL5 from cytoplasm requires its direct interaction with LIN9 and is essential for male meiosis and fertility.

First Author  Zhang X Year  2021
Journal  PLoS Genet Volume  17
Issue  8 Pages  e1009753
PubMed ID  34388164 Mgi Jnum  J:324057
Mgi Id  MGI:6755069 Doi  10.1371/journal.pgen.1009753
Citation  Zhang X, et al. (2021) Nuclear translocation of MTL5 from cytoplasm requires its direct interaction with LIN9 and is essential for male meiosis and fertility. PLoS Genet 17(8):e1009753
abstractText  Meiosis is essential for the generation of gametes and sexual reproduction, yet the factors and underlying mechanisms regulating meiotic progression remain largely unknown. Here, we showed that MTL5 translocates into nuclei of spermatocytes during zygotene-pachytene transition and ensures meiosis advances beyond pachytene stage. MTL5 shows strong interactions with MuvB core complex components, a well-known transcriptional complex regulating mitotic progression, and the zygotene-pachytene transition of MTL5 is mediated by its direct interaction with the component LIN9, through MTL5 C-terminal 443-475 residues. Male Mtl5c-mu/c-mu mice expressing the truncated MTL5 (p.Ser445Arg fs*3) that lacks the interaction with LIN9 and is detained in cytoplasm showed male infertility and spermatogenic arrest at pachytene stage, same as that of Mtl5 knockout mice, indicating that the interaction with LIN9 is essential for the nuclear translocation and function of MTL5 during meiosis. Our data demonstrated MTL5 translocates into nuclei during the zygotene-pachytene transition to initiate its function along with the MuvB core complex in pachytene spermatocytes, highlighting a new mechanism regulating the progression of male meiosis.
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