ArticleCell death and differentiation2026
Male specific conserved LncRNA TSCL1 regulated target mRNA translation by interaction with PIWIL1.
Article in Cell death and differentiation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Long non-coding RNAs (lncRNAs) play crucial roles in diverse mammalian physiological processes, yet their functions in spermatogenesis remain largely underexplored. Here, we identify a unique class of conserved haploid spermatid-associated lncRNAs (cHS-LncRNAs) defined by sequence conservation, testis-restricted expression, and elevated levels in haploid spermatids. Among these, testis-specific conserved lncRNA 1 (Tscl1) is the most highly expressed in round spermatids. Tscl1-null male mice exhibit reduced sperm motility, disorganized mitochondrial sheaths, abnormal fatty acid metabolism, and complete infertility. Mechanistically, Tscl1 directly binds PIWIL1 and HuR via its 5' stem-loop and multiple AU-rich elements, respectively. This interaction promotes assembly of a PIWIL1/eIF3f/HuR/eIF4G3 complex that enhances translation of fatty-acid-metabolism-related mRNAs within the chromatoid body. Notably, TSCL1 variants disrupting the PIWIL1-binding region are significantly enriched in patients with non-obstructive azoospermia (NOA) compared to fertile controls. Collectively, our findings uncover a critical role for Tscl1 in modulating translation during spermiogenesis and implicate TSCL1 as a potential pathogenic locus in human male infertility.
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