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Adv."],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:p>Pericentric heterochromatin serves as a fundamental component of eukaryotic chromosomes, endowing specialized genomic architecture with broad functional consequences. Although it is universally marked by H3K9me3 modification, the underlying pericentric DNA sequences diverge substantially across species. Here, by leveraging a transposition reporter system combined with a genome-wide RNA interference (RNAi) screen, we identified a specialized mechanism for recruiting SUV39H methyltransferase to initiate pericentric heterochromatin formation. This pathway depends on a highly ordered complex comprising the Puf68, pre\u2013transfer RNAs (tRNAs), and the primer binding site (PBS). Puf68 binds with high affinity to poly-U tracts in pre-tRNA 3\u2032 trailer, forming a Puf68\/pre-tRNA complex that subsequently base-pairs with the PBS of nascent long terminal repeat (LTR)\u2013retrotransposons. Through direct interaction, Puf68 recruits Su(var)3-9 to these regions, catalyzing H3K9 trimethylation. Notably, Puf68 is sufficient to initiate de novo heterochromatin assembly both at pericentric and ectopically integrated LTR-retrotransposon regions. Our findings not only uncover a previously unrecognized mechanism of heterochromatin initiation but also resolve a long-standing question of how hosts harness nascent LTR-retrotransposon transcripts.<\/jats:p>","DOI":"10.1126\/sciadv.aef2333","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:59:26Z","timestamp":1788371966000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Hijacking pre-tRNA enables LTR-retrotransposon\u2013initiated constitutive heterochromatin formation"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9895-5827","authenticated-orcid":true,"given":"Yazi","family":"Deng","sequence":"first","affiliation":[{"name":"State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1514-722X","authenticated-orcid":true,"given":"Yu","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Ni","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoqi","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5164-2765","authenticated-orcid":true,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2356-6245","authenticated-orcid":true,"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"E. 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