TheStk35locus contributes to normal gametogenesis and encodes a lncRNA responsive to oxidative stress

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 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.

Coronary artery disease: differential expression of ceRNAs and interaction analyses

“…By ranking the top 15 nodes in our ceRNA network by degree centrality, we identified a range of significant ceRNA interactions in CAD (see Table 2); these findings concurred with previous literature (see Table 4) (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). It was evident from our results that several ceRNAs were related to cardiovascular diseases.…”

“…STK35 may act as a central kinase linking the actin stress fibers, cell cycle progression, migration of endothelial cells, and survival. Its protein constitutive overexpression enhances caspase-independent cell death under oxidative stress conditions (44)(45)(46) NA indicates no data available. BMP2, bone morphogenetic protein 2; ceRNA, competitive endogenous RNA; KLF12, Krüppel like factor 12; NACC2, nucleus accumbens associated 2; PSMA3, proteasome subunit alpha type-3; STK35, serine/threonine kinase 35.…”

“…Specifically, the interaction between STK35L1 and nuclear actin may be critical in the regulation of these fundamental endothelial functions (45). Serine/threonine kinase 35 (STK35) is a recently identified human kinase that plays a key role in autophosphorylation, which is functionally linked with actin stress fibers, cell cycle progression, and survival (see Table 4) (46). Microarray analysis previously showed that nuclearretained importin α2 binds with DNase I-sensitive nuclear component(s) and controls the selective upregulation of mRNA encoding STK35.…”

STK35L1 regulates Plasmodium infection and expression of cell cycle genes during liver stage of malaria

“…Moreover, in endothelial cells, the silencing of the STK35L1gene drastically impaired cell migration 9 . A study showed that importin-a2 enhanced the expression of the stk35l1gene, and constitutive overexpression of STK35L1 activates caspase-independent cell death under oxidative stress conditions 10 .STK35 (STK35L1) knockout mice showed defects in eye development and were infertile 11 . STK35L1 transcript was altered in colorectal cancer and cardiomyopathy 12,13 .…”