Male germ cells are uniquely sensitive to thermal stress, which can impair spermatogenesis and compromise fertility. To elucidate the early molecular responses to heat in male germ cells, we previously profiled transcriptomic changes in round spermatids isolated following testicular hyperthermia.
We identified the long non-coding RNA 4930555K19Rik as the most significantly upregulated transcript and confirmed concurrent induction in spermatocytes. Using pull-down assays 4930555K19Rik, was shown to interact with Far upstream element-binding protein 1 (FUBP1), a transcriptional regulator of cell cycle progression. In accordance with this, overexpression of 4930555K19Rik in mouse melanoma cells led to cell cycle inhibition, the same phenotype observed upon FUBP1 disruption. To understand this further, we looked at expression of two genes supressed by FUBP1 activity, namely Cdkn1a (p21) and Trp53 (p53). Overexpression of 4930555K19Rik in somatic cells led to significant upregulation of both genes, suggesting functional impairment of FUBP1. Furthermore, in male germ cells, the FUBP1-regulated gene Ccna1 essential for meiotic progression, was significantly downregulated in spermatocytes 6 hours after heat stress.
These findings implicate a novel role of 4930555K19Rik as a potential inhibitor of FUBP1 function, which has implications in the male germ cell heat stress response, causing cell cycle arrest.