tRNA-derived fragments (tRFs) regulate post-transcriptional gene expression via AGO-dependent mechanism in IL-1β stimulated chondrocytes
Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved..
OBJECTIVES: Recent studies have shown that tRNA-derived RNA fragments (tRFs) are novel regulators of post-transcriptional gene expression. However, the expression profiles and their role in post-transcriptional gene regulation in chondrocytes is unknown. Here, we determined tRFs expression profile and explored tRF-3003a role in post-transcriptional gene regulation in IL-1β stimulated chondrocytes.
METHODS: We used qPCR arrays to determine tRNAs and tRFs expression in age- and sex-matched primary human OA chondrocytes and TC28/I2 cells stimulated with IL-1β. Chondrocytes were transfected with tRNA-CysGCA overexpression plasmid or tRF-3003a mimic and 3'UTR luciferase reporter plasmids of mRNAs harboring predicted tRF target "seed sequence". The AGO-RNA-induced silencing complex (AGO-RISC)-dependent repressive activity of tRF-3003a was determined by siRNA-mediated knockdown of AGO2.
RESULTS: IL-1β increased the expression levels of specific tRNAs and of tRF-3003a, a type 3 tRF produced by the cleavage of tRNA-CysGCA. tRF-3003a "seed sequence" was identified in the 3'UTR of JAK3 mRNA and tRNA-CysGCA overexpression or transfection of a tRF-3003a mimic in chondrocytes downregulated JAK3 expression and significantly reduced the activity of the 3'UTR reporter. RIP assay showed enrichment of tRF-3003a into AGO2/RISC in IL-1β treated chondrocytes. The suppressive effect of tRF-3003a on JAK3 3'UTR reporter was abrogated with siRNA-mediated depletion of AGO2.
CONCLUSIONS: We demonstrate that under pathological conditions chondrocytes display perturbations in the expression profile of specific tRNAs and tRFs. Furthermore, a specific tRF namely tRF-3003a can post-transcriptionally regulate JAK3 expression via AGO/RISC formation in chondrocytes. Identification of this novel mechanism may be of value in the design of precision therapies for OA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Osteoarthritis and cartilage - 28(2020), 8 vom: 15. Aug., Seite 1102-1110 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Green, J A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.07.2021 Date Revised 05.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.joca.2020.04.014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309906881 |
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| 100 | 1 | |a Green, J A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a tRNA-derived fragments (tRFs) regulate post-transcriptional gene expression via AGO-dependent mechanism in IL-1β stimulated chondrocytes |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 26.07.2021 | ||
| 500 | |a Date Revised 05.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a OBJECTIVES: Recent studies have shown that tRNA-derived RNA fragments (tRFs) are novel regulators of post-transcriptional gene expression. However, the expression profiles and their role in post-transcriptional gene regulation in chondrocytes is unknown. Here, we determined tRFs expression profile and explored tRF-3003a role in post-transcriptional gene regulation in IL-1β stimulated chondrocytes | ||
| 520 | |a METHODS: We used qPCR arrays to determine tRNAs and tRFs expression in age- and sex-matched primary human OA chondrocytes and TC28/I2 cells stimulated with IL-1β. Chondrocytes were transfected with tRNA-CysGCA overexpression plasmid or tRF-3003a mimic and 3'UTR luciferase reporter plasmids of mRNAs harboring predicted tRF target "seed sequence". The AGO-RNA-induced silencing complex (AGO-RISC)-dependent repressive activity of tRF-3003a was determined by siRNA-mediated knockdown of AGO2 | ||
| 520 | |a RESULTS: IL-1β increased the expression levels of specific tRNAs and of tRF-3003a, a type 3 tRF produced by the cleavage of tRNA-CysGCA. tRF-3003a "seed sequence" was identified in the 3'UTR of JAK3 mRNA and tRNA-CysGCA overexpression or transfection of a tRF-3003a mimic in chondrocytes downregulated JAK3 expression and significantly reduced the activity of the 3'UTR reporter. RIP assay showed enrichment of tRF-3003a into AGO2/RISC in IL-1β treated chondrocytes. The suppressive effect of tRF-3003a on JAK3 3'UTR reporter was abrogated with siRNA-mediated depletion of AGO2 | ||
| 520 | |a CONCLUSIONS: We demonstrate that under pathological conditions chondrocytes display perturbations in the expression profile of specific tRNAs and tRFs. Furthermore, a specific tRF namely tRF-3003a can post-transcriptionally regulate JAK3 expression via AGO/RISC formation in chondrocytes. Identification of this novel mechanism may be of value in the design of precision therapies for OA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chondrocyte | |
| 650 | 4 | |a JAK3 | |
| 650 | 4 | |a Noncoding RNA | |
| 650 | 4 | |a Osteoarthritis | |
| 650 | 4 | |a Transfer RNA | |
| 650 | 4 | |a tRNA-derived fragments | |
| 650 | 7 | |a 3' Untranslated Regions |2 NLM | |
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| 650 | 7 | |a Interleukin-1beta |2 NLM | |
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| 700 | 1 | |a Ansari, M Y |e verfasserin |4 aut | |
| 700 | 1 | |a Ball, H C |e verfasserin |4 aut | |
| 700 | 1 | |a Haqqi, T M |e verfasserin |4 aut | |
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