The STK35 locus contributes to normal gametogenesis and encodes a lncRNA responsive to oxidative stress

Autor: Yoichi Miyamoto, Penny A. F. Whiley, Hoey Y. Goh, Chin Wong, Gavin Higgins, Taro Tachibana, Paul G. McMenamin, Lynne Mayne, Kate L. Loveland
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Biology Open, Vol 7, Iss 8 (2018)
Druh dokumentu: article
ISSN: 2046-6390
DOI: 10.1242/bio.032631
Popis: Serine/threonine kinase 35 (STK35) is a recently identified human kinase with an autophosphorylation function, linked functionally to actin stress fibers, cell cycle progression and survival. STK35 has previously been shown to be highly expressed in human testis, and we demonstrated its regulation by nuclear-localized importin α2 in HeLa cells. The present study identifies progressive expression from the STK35 locus of two coding mRNA isoforms and one long non-coding RNA (lncRNA) in mouse testis during spermatogenesis, indicating their tightly controlled synthesis. Additionally, lncRNA transcripts are increased by exposure to oxidative stress in mouse GC-1 germ cell line. STK35 knockout (KO) mice lacking all three RNAs are born at sub-Mendelian frequency, and adults manifest both male and female germline deficiency. KO males exhibit no or partial spermatogenesis in most testis tubule cross-sections; KO ovaries are smaller and contain fewer follicles. Eyes of KO mice display phenotypes ranging from gross deformity to mild goniodysgenesis or iridocorneal angle malformation, to overtly normal. These findings demonstrate the tight regulation of transcription from the STK35 locus and its central importance to fertility, eye development and cell responses to oxidative stress.
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