Biology subjects

Schorn, A. J.

Publications and source records attributed to Schorn, A. J..

3 recordsLinked to original sources

bioRxiv2026

3'-tRNA Fragments Target Domesticated LTR-Retrotransposons

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.

molecular biology↗

bioRxiv2025

HENMT1 restricts endogenous retrovirus activity by methylation of 3'-tRNA fragments

Long terminal repeat (LTR) retroelements such as endogenous retroviruses (ERVs) utilize host tRNA as a primer for reverse transcription, and are thus susceptible to silencing by small RNAs derived from the 3'-end of mature tRNAs (3'-tRFs). Rigorous quantification reveals that 3-tRF amounts are not directly proportional to tRNA levels, instead, 3-tRFs of specific isodecoder tRNAs are highly enriched in a pattern conserved between mouse and human. We found that 3-tRFs are 2-O methylated by the small RNA methyltransferase HENMT1 protecting them from degradation and promoting ERV silencing. In the absence of HENMT1, 3-tRFs are subjected to non-templated tailing by the terminal nucleotidyltransferases TUT4 and TENT2 that regulate small RNA turnover. Due to the perfect sequence complementarity of 3-tRFs to endogenous retroviral sequences, they have thousands of targets in mammalian genomes. We conducted a massively parallel reporter assay using Mus musculus particle type D, a highly active murine ERV, to determine target site rules for 3-tRFs. Our results suggest that HENMT1 not only stabilizes germline integrity but also serves transposon control by 3-tRFs in the soma.

molecular biology↗

bioRxiv2023

Pseudouridine guides germline small RNA transport and epigenetic inheritance

Epigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes1. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation2,3. In C. elegans, these inherited small RNAs have poly (UG) tails4, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine ({Psi}) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop novel assays to detect {Psi} in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs and their precursors. We also detect substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) in Arabidopsis pollen, and piwi-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are localized to sperm cells, and we found that PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with {Psi} and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that Exportin-t is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, {Psi} has a conserved role in marking inherited small RNAs in the germline. One-Sentence SummaryPseudouridine marks germline small RNAs in plants and mammals, impacting epigenetic inheritance via nuclear transport.

genetics↗