Biology subjects

Peacey, M.

Publications and source records attributed to Peacey, M..

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

Mechanism of an alternative splicing switch mediated by cell-specific and general splicing regulators

Alternative pre-mRNA splicing is regulated by RNA binding proteins (RBPs) that activate or repress regulated splice sites. Repressive RBPs bind stably to target RNAs via multivalent interactions, which can be achieved by both homo-oligomerization and by interactions with other RBPs mediated by intrinsically disordered regions (IDRs). Cell-specific splicing decisions commonly involve the action of widely expressed RBPs that can bind around target exons, but without effect in the absence of a key cell-specific regulator. To address how cell-specific regulators collaborate with constitutive RBPs in alternative splicing regulation we used the smooth-muscle specific regulator RBPMS. Recombinant RBPMS is sufficient to switch cell specific alternative splicing of Tpm1 exon 3 in cell free assays by remodelling ribonucleprotein complexes and preventing assembly of ATP-dependent splicing complexes. This activity depends upon its C-terminal IDR, which facilitates dynamic higher-order self-assembly, cooperative binding to multivalent RNA, and interactions with other splicing co-regulators, including MBNL1 and RBFOX2. Our data show how a cell-specific RBP can co-opt more widely expressed regulatory RBPs to facilitate cooperative assembly of stable cell-specific regulatory complexes.

molecular biology↗