Steinberg, Josh I, Sertznig, Helene, Desmarais, John J, Wilken, Jenna, Rubio, Daisy, Peacey, Matthew, Kinney, Justin B, Schorn, Andrea J (May 2025) HENMT1 restricts endogenous retrovirus activity by methylation of 3'-tRNA fragments. bioRxiv. ISSN 2692-8205 (Public Dataset) (Submitted)
Abstract
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 tRNA level are not directly proportional to 3'-tRFs but specific isoacceptor and isodecoder sequences are highly enriched in a pattern conserved between mouse and human. We found 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.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation 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 organism description > virus > retrovirus organism description > virus |
| CSHL Authors: | |
| Communities: | CSHL labs > Kinney lab CSHL labs > Martienssen lab CSHL labs > Schorn lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 12 May 2025 |
| Date Deposited: | 17 Jun 2025 12:18 |
| Last Modified: | 17 Jun 2025 12:18 |
| PMCID: | PMC12132306 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/41888 |
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