The TENT5A-ATXN2 axis modulates germline and somatic cell survival during heat stress.

Abstract

Stress conditions elicit the formation of different kinds of stress granules (SGs). Although male germ cells are particularly sensitive to heat stress, the composition of heat-induced SGs in the testis remains poorly characterized. Here, we show that ATXN2 is a main component of heat-induced SGs in male germ cells and identify a unique population of ATXN2-positive SGs in leptotene and zygotene spermatocytes lacking classical SG markers. The terminal nucleotidyltransferase 5A (TENT5A) is a cytoplasmic poly(A) polymerase that extends the poly(A) tails of mRNAs. Tent5a mRNA expression increases when somatic and germ cells are exposed to 42 °C, but not upon exposure to other stressors. In vitro, TENT5A extends the poly(A) tail of Atxn2 transcripts, stabilizing them while repressing their translation. In heat-stressed testes, TENT5A depletion increases ATXN2-positive granules and reduces apoptosis in late pachytene spermatocytes. Thus, enhanced stress resilience in Tent5a-depleted male germ cells preserves spermatogenesis and rescues fertility following heat exposure.