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Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression

BACKGROUND: Transcriptomics, such as that of non-coding RNA (ncRNA), which include microRNA (miRNA), circular RNA, and the transfer RNA (tRNA)-derived fragments (tiRNA and tRF) in Alzheimer’s disease (AD) have attracted much attention recently. The tiRNA and tRFs are produced when the tRNA splits at...

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Autores principales: Lu, Honglin, Liu, Lin, Han, Shu, Wang, Binbin, Qin, Jin, Bu, Kailin, Zhang, Yingzhen, Li, Zhongzhong, Ma, Lina, Tian, Jing, Zhang, Kun, Li, Tong, Cui, Huixian, Liu, Xiaoyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506760/
https://www.ncbi.nlm.nih.gov/pubmed/34734009
http://dx.doi.org/10.21037/atm-21-4318
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author Lu, Honglin
Liu, Lin
Han, Shu
Wang, Binbin
Qin, Jin
Bu, Kailin
Zhang, Yingzhen
Li, Zhongzhong
Ma, Lina
Tian, Jing
Zhang, Kun
Li, Tong
Cui, Huixian
Liu, Xiaoyun
author_facet Lu, Honglin
Liu, Lin
Han, Shu
Wang, Binbin
Qin, Jin
Bu, Kailin
Zhang, Yingzhen
Li, Zhongzhong
Ma, Lina
Tian, Jing
Zhang, Kun
Li, Tong
Cui, Huixian
Liu, Xiaoyun
author_sort Lu, Honglin
collection PubMed
description BACKGROUND: Transcriptomics, such as that of non-coding RNA (ncRNA), which include microRNA (miRNA), circular RNA, and the transfer RNA (tRNA)-derived fragments (tiRNA and tRF) in Alzheimer’s disease (AD) have attracted much attention recently. The tiRNA and tRFs are produced when the tRNA splits at specific sites. The expression change and related function of tiRNA and tRFs in AD has not been fully investigated. METHODS: In our study, APP/PS1 transgenic mice (AD mice model) and healthy control mice were used to discover the differentially expressed tiRNA and tRFs with high-throughput sequencing. Among the differentially expressed tiRNA and tRFs, we chose two tRFs (tRF-Thr-CGT-003 and tRF-Leu-CAA-004) and predicted the target messenger RNAs (mRNAs) with miRanda and Target Scan. The target mRNAs of tRF-related function and pathways were analyzed, then we performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot to validate the related target mRNAs and pathways. RESULTS: A total of 27 significantly different tiRNA and tRFs were detected between wild type (WT) and APP/PS1 groups, including 14 up-regulated and 13 down-regulated. Through analyzing the target mRNAs of all differentially expressed tiRNA and tRFs with GO enrichment, we found the target mRNAs could take part in the learning and memory biological process, synapse organization, cognition biological process, synaptic transmission, amyloid-β (Aβ) metabolic process, and so on. We then chose three differentially expressed tRFs for further qPCR validation and passed two tRFs: tRF-Thr-CGT-003 and tRF-Leu-CAA-004, that were found to regulate the calcium regulation-related proteins (the voltage-gated calcium channel γ2 subunit and the RYR1 endoplasmic reticulum calcium released protein) and the retinol metabolism-related proteins (retinoic acid metabolic enzymes CYP2S1, CYP2C68, CYP2S1). CONCLUSIONS: The APP expression and presenilin mutation in APP/PS1 mice could cause tiRNA and tRFs expression change. Among the differentially expressed tiRNA and tRFs, we found some tRFs took part in the voltage-gated calcium channel γ2 subunit expression and regulation, influencing the neuron calcium homeostasis. Moreover, we also found the tRFs may participate in the regulation of retinol metabolism. Our findings suggest that the dysregulated tiRNA and tRFs may be beneficially exploited as potential diagnostic biomarkers and/or therapeutic targets of AD.
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spelling pubmed-85067602021-11-02 Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression Lu, Honglin Liu, Lin Han, Shu Wang, Binbin Qin, Jin Bu, Kailin Zhang, Yingzhen Li, Zhongzhong Ma, Lina Tian, Jing Zhang, Kun Li, Tong Cui, Huixian Liu, Xiaoyun Ann Transl Med Original Article BACKGROUND: Transcriptomics, such as that of non-coding RNA (ncRNA), which include microRNA (miRNA), circular RNA, and the transfer RNA (tRNA)-derived fragments (tiRNA and tRF) in Alzheimer’s disease (AD) have attracted much attention recently. The tiRNA and tRFs are produced when the tRNA splits at specific sites. The expression change and related function of tiRNA and tRFs in AD has not been fully investigated. METHODS: In our study, APP/PS1 transgenic mice (AD mice model) and healthy control mice were used to discover the differentially expressed tiRNA and tRFs with high-throughput sequencing. Among the differentially expressed tiRNA and tRFs, we chose two tRFs (tRF-Thr-CGT-003 and tRF-Leu-CAA-004) and predicted the target messenger RNAs (mRNAs) with miRanda and Target Scan. The target mRNAs of tRF-related function and pathways were analyzed, then we performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot to validate the related target mRNAs and pathways. RESULTS: A total of 27 significantly different tiRNA and tRFs were detected between wild type (WT) and APP/PS1 groups, including 14 up-regulated and 13 down-regulated. Through analyzing the target mRNAs of all differentially expressed tiRNA and tRFs with GO enrichment, we found the target mRNAs could take part in the learning and memory biological process, synapse organization, cognition biological process, synaptic transmission, amyloid-β (Aβ) metabolic process, and so on. We then chose three differentially expressed tRFs for further qPCR validation and passed two tRFs: tRF-Thr-CGT-003 and tRF-Leu-CAA-004, that were found to regulate the calcium regulation-related proteins (the voltage-gated calcium channel γ2 subunit and the RYR1 endoplasmic reticulum calcium released protein) and the retinol metabolism-related proteins (retinoic acid metabolic enzymes CYP2S1, CYP2C68, CYP2S1). CONCLUSIONS: The APP expression and presenilin mutation in APP/PS1 mice could cause tiRNA and tRFs expression change. Among the differentially expressed tiRNA and tRFs, we found some tRFs took part in the voltage-gated calcium channel γ2 subunit expression and regulation, influencing the neuron calcium homeostasis. Moreover, we also found the tRFs may participate in the regulation of retinol metabolism. Our findings suggest that the dysregulated tiRNA and tRFs may be beneficially exploited as potential diagnostic biomarkers and/or therapeutic targets of AD. AME Publishing Company 2021-09 /pmc/articles/PMC8506760/ /pubmed/34734009 http://dx.doi.org/10.21037/atm-21-4318 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Lu, Honglin
Liu, Lin
Han, Shu
Wang, Binbin
Qin, Jin
Bu, Kailin
Zhang, Yingzhen
Li, Zhongzhong
Ma, Lina
Tian, Jing
Zhang, Kun
Li, Tong
Cui, Huixian
Liu, Xiaoyun
Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression
title Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression
title_full Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression
title_fullStr Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression
title_full_unstemmed Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression
title_short Expression of tiRNA and tRF in APP/PS1 transgenic mice and the change of related proteins expression
title_sort expression of tirna and trf in app/ps1 transgenic mice and the change of related proteins expression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506760/
https://www.ncbi.nlm.nih.gov/pubmed/34734009
http://dx.doi.org/10.21037/atm-21-4318
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