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

Yoichi Miyamoto, Penelope A.F Whiley, Hoey Goh, Chin Long Wong, Taro Tachibana, Paul Gerard McMenamin, Lynne Mayne, Katherine Ann Lakoski Loveland

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 noncoding 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.

Original languageEnglish
Article numberbio032631
Number of pages12
JournalBiology Open
Volume7
Issue number8
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Eye development
  • Hydrogen peroxide
  • Long non-coding RNA
  • Oogenesis
  • Spermatogenesis

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