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

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 nucl...

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Bibliographic Details
Published in:Biology open 2018, Vol.7 (8)
Main Authors: Miyamoto, Yoichi, Whiley, Penny A F, Goh, Hoey Y, Wong, Chin, Higgins, Gavin, Tachibana, Taro, McMenamin, Paul G, Mayne, Lynne, Loveland, Kate L
Format: Article
Language:English
Subjects:
Actin
Cell cycle
Cell survival
Eye development
Fertility
Fibers
Follicles
Gametogenesis
Gene regulation
Hydrogen peroxide
Isoforms
Kinases
Loci
Long non-coding RNA
Non-coding RNA
Oogenesis
Ovaries
Oxidative stress
Phenotypes
Protein-serine/threonine kinase
Spermatogenesis
Testes
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Summary: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.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.032631