Charmant Olivia, Gruchota Julita, Arnaiz Olivier, Nowak Katarzyna P, Moisan Nicolas, Zangarelli Coralie, Bétermier Mireille, Anielska-Mazur Anna, Legros Véronique, Chevreux Guillaume, Nowak Jacek K, Duharcourt Sandra
Université Paris Cité, CNRS, Institut Jacques Monod, 15 rue Hélène Brion, F-75013 Paris, France.
Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland.
Nucleic Acids Res. 2025 Jan 7;53(1). doi: 10.1093/nar/gkae1055.
Ciliates undergo developmentally programmed genome elimination, in which small RNAs direct the removal of transposable elements (TEs) during the development of the somatic nucleus. Twenty-five nucleotide scanRNAs (scnRNAs) are produced from the entire germline genome and transported to the maternal somatic nucleus, where selection of scnRNAs corresponding to germline-specific sequences is thought to take place. Selected scnRNAs then guide the elimination of TEs in the developing somatic nucleus. How germline-specific scnRNAs are selected remains to be determined. Here, we provide important mechanistic insights into the scnRNA selection pathway by identifying a Paramecium homolog of Gtsf1 as essential for the selective degradation of scnRNAs corresponding to retained somatic sequences. Consistently, we also show that Gtsf1 is localized in the maternal somatic nucleus where it associates with the scnRNA-binding protein Ptiwi09. Furthermore, we demonstrate that the scnRNA selection process is critical for genome elimination. We propose that Gtsf1 is required for the coordinated degradation of Ptiwi09-scnRNA complexes that pair with target RNA via the ubiquitin pathway, similarly to the mechanism suggested for microRNA target-directed degradation in metazoans.
纤毛虫经历发育程序控制的基因组消除过程，在此过程中，小RNA在体细胞核发育期间指导转座元件（TEs）的去除。25个核苷酸的扫描RNA（scnRNAs）由整个种系基因组产生，并被转运到母体体细胞核，在那里，对应于种系特异性序列的scnRNAs的选择被认为会发生。然后，被选择的scnRNAs指导发育中的体细胞核中TEs的消除。种系特异性scnRNAs是如何被选择的仍有待确定。在这里，我们通过鉴定Gtsf1的草履虫同源物，为scnRNA选择途径提供了重要的机制见解，该同源物对于与保留的体细胞序列相对应的scnRNAs的选择性降解至关重要。一致地，我们还表明Gtsf1定位于母体体细胞核中，在那里它与scnRNA结合蛋白Ptiwi09相关联。此外，我们证明scnRNA选择过程对于基因组消除至关重要。我们提出，Gtsf1是通过泛素途径与靶RNA配对的Ptiwi09 - scnRNA复合物协调降解所必需的，这类似于后生动物中微小RNA靶标定向降解所提出的机制。
