Miyamoto Yoichi, Whiley Penny A F, Goh Hoey Y, Wong Chin, Higgins Gavin, Tachibana Taro, McMenamin Paul G, Mayne Lynne, Loveland Kate L
Department of Biochemistry and Molecular Biology, School of Biological Sciences, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
Biol Open. 2018 Aug 6;7(8):bio032631. doi: 10.1242/bio.032631.
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. 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 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. 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 locus and its central importance to fertility, eye development and cell responses to oxidative stress.
丝氨酸/苏氨酸激酶35（STK35）是一种最近发现的具有自磷酸化功能的人类激酶，在功能上与肌动蛋白应激纤维、细胞周期进程和细胞存活相关。此前已证明它在人类睾丸中高度表达，并且我们在HeLa细胞中证实了其受核定位的输入蛋白α2调控。本研究确定了在小鼠睾丸精子发生过程中，从该基因座逐渐表达出两种编码mRNA异构体和一种长链非编码RNA（lncRNA），这表明它们的合成受到严格控制。此外，在小鼠GC-1生殖细胞系中，暴露于氧化应激会增加lncRNA转录本。缺乏所有这三种RNA的基因敲除（KO）小鼠以低于孟德尔频率出生，成年后表现出雄性和雌性生殖系缺陷。基因敲除雄性小鼠在大多数睾丸小管横切面上无精子发生或仅有部分精子发生；基因敲除雌性小鼠的卵巢较小且卵泡较少。基因敲除小鼠的眼睛表现出从严重畸形到轻度前房角发育异常或虹膜角膜角畸形，再到外观正常的一系列表型。这些发现证明了该基因座转录的严格调控及其对生育、眼睛发育和细胞对氧化应激反应的核心重要性。
