3'-tRNA Fragments Target Domesticated LTR-Retrotransposons

Peacey, Matthew, Steinberg, Joshua I, Schorn, Andrea J (January 2026) 3'-tRNA Fragments Target Domesticated LTR-Retrotransposons. bioRxiv. ISSN 2692-8205 (Submitted)

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Abstract

Long terminal repeat (LTR) retrotransposons have been extensively co-opted by their mammalian hosts and serve essential functions. 3’-tRNA fragments (3’-tRFs) mediate post-transcriptional repression of active, murine LTR-retrotransposons through complementarity to their highly conserved tRNA primer binding site (PBS). Here, we found that 3’-tRF target sites derived from the PBS are widespread in retrotransposon-derived transcripts, suggesting that domesticated elements remain subject to regulation. Using luciferase reporters, we validated post-transcriptional repression at multiple 5’ UTR sites derived from LTR-retrotransposons. We further established paternally expressed 3 (Peg3), an imprinted gene with homology to retroviral Gag, as a target of an Arg-TCT 3’-tRF via a conserved 5’ UTR site. These findings provide a proof-of-principle for regulation of domesticated LTR-retrotransposons by 3’-tRFs, suggesting that their ancient role in transposon defense has been co-opted for endogenous gene regulation.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons
CSHL Authors:
Communities: CSHL labs > Martienssen lab
CSHL labs > Schorn lab
School of Biological Sciences > Publications
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 22 January 2026
Date Deposited: 30 Jun 2026 18:42
Last Modified: 30 Jun 2026 18:42
PMCID: PMC12853362
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42242

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