Ilık İbrahim Avşar, Yang Xu, Zhang Z Z Zhao, Aktaş Tuğçe
Otto Warburg Laboratories, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Nat Rev Mol Cell Biol. 2025 Jun 30. doi: 10.1038/s41580-025-00867-8.
Nearly half of the genome of humans and other mammals consists of transposable elements (TEs). Recent advancements in sequencing technologies have revealed that TEs have important regulatory functions, echoing Barbara McClintock's 1950s vision of TEs as 'controlling elements'. Nevertheless, TEs can still interfere with gene expression and are linked to various human diseases. In this Review, we first discuss the multilayered transcriptional and post-transcriptional defence mechanisms that repress TE activity, and examine how they regulate endogenous gene expression. We then discuss recent studies showing that TEs can escape these repression mechanisms and unexpectedly become a vital part of animal development. Finally, we explore findings on TE derepression in cancer and neurological diseases, and emerging therapeutic strategies that exploit TE derepression, such as immunotherapies that target TE-derived tumour-specific antigens.
人类和其他哺乳动物的基因组中近一半由转座元件（TEs）组成。测序技术的最新进展表明，TEs具有重要的调控功能，这呼应了芭芭拉·麦克林托克在20世纪50年代将TEs视为“控制元件”的观点。然而，TEs仍然会干扰基因表达，并与多种人类疾病相关联。在本综述中，我们首先讨论抑制TE活性的多层转录和转录后防御机制，并研究它们如何调节内源性基因表达。然后，我们讨论最近的研究，这些研究表明TEs可以逃避这些抑制机制，并意外地成为动物发育的重要组成部分。最后，我们探讨癌症和神经疾病中TE去抑制的研究结果，以及利用TE去抑制的新兴治疗策略，例如针对TE衍生的肿瘤特异性抗原的免疫疗法。
