Sobinoff Alexander P, Wells Jadon K, Chow Maurice, Nelson Christopher B, Wu Xinyi, Cohen Scott B, Lau Yu Heng, Bryan Tracy M, Fox Archa, Pickett Hilda A
Telomere Length Regulation Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
School of Chemistry, The University of Sydney, Camperdown, NSW, Australia.
Nat Commun. 2025 Jul 1;16(1):5769. doi: 10.1038/s41467-025-60924-w.
Telomerase is a ribonucleoprotein enzyme that maintains telomeric repeats on chromosome ends in continuously dividing cells. Telomere maintenance via telomerase is dependent on the correct assembly of the enzyme complex, complex stabilization by associated cofactors, and effective recruitment to the telomere. Here, we show that telomerase is regulated in each of these processes by the Drosophila behaviour/human splicing (DBHS) family of RNA/DNA binding proteins (NONO, SFPQ and PSPC1). The DBHS proteins associate with catalytically active telomerase through the hTR RNA template component. Cells lacking the DBHS proteins display telomerase retention in nuclear Cajal bodies and impaired telomerase recruitment to the telomere, with NONO and PSPC1 depletion culminating in progressive telomere shortening in several cell lines, with the exception of long-term NONO depletion in 293 and 293T. Our results reveal the DBHS protein family as components of the telomerase trafficking machinery integral to telomere maintenance.
端粒酶是一种核糖核蛋白酶，可在持续分裂的细胞中维持染色体末端的端粒重复序列。通过端粒酶进行的端粒维持依赖于酶复合物的正确组装、相关辅因子对复合物的稳定作用以及端粒酶向端粒的有效募集。在此，我们表明，果蝇行为/人类剪接（DBHS）家族的RNA/DNA结合蛋白（NONO、SFPQ和PSPC1）在上述每个过程中对端粒酶进行调控。DBHS蛋白通过hTR RNA模板成分与具有催化活性的端粒酶结合。缺乏DBHS蛋白的细胞表现出端粒酶滞留在核卡哈尔体中，且端粒酶向端粒的募集受损，除了在293和293T细胞中长期缺失NONO外，NONO和PSPC1的缺失最终导致几种细胞系中端粒逐渐缩短。我们的结果揭示了DBHS蛋白家族是端粒维持所必需的端粒酶运输机制的组成部分。
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