A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick

Small regulatory RNAs (sRNAs) are involved in antiviral defense and gene regulation. Although roles of RNA-dependent RNA Polymerases (RdRPs) in sRNA biology are extensively studied in nematodes, plants and fungi, understanding of RdRP homologs in other animals is still lacking. Here, we study sRNAs...

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Main Authors: Feng, Canran, Torimaru, Kyosuke, Lim, Mandy Yu Theng, Chak, Li-Ling, Shiimori, Masami, Tsuji, Kosuke, Tanaka, Tetsuya, Iida, Junko, Okamura, Katsutomo
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/169716
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spelling sg-ntu-dr.10356-1697162023-08-07T15:31:57Z A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick Feng, Canran Torimaru, Kyosuke Lim, Mandy Yu Theng Chak, Li-Ling Shiimori, Masami Tsuji, Kosuke Tanaka, Tetsuya Iida, Junko Okamura, Katsutomo School of Biological Sciences Temasek Life Sciences Laboratory Science::Biological sciences Small Interfering RNA Eukaryote Small regulatory RNAs (sRNAs) are involved in antiviral defense and gene regulation. Although roles of RNA-dependent RNA Polymerases (RdRPs) in sRNA biology are extensively studied in nematodes, plants and fungi, understanding of RdRP homologs in other animals is still lacking. Here, we study sRNAs in the ISE6 cell line, which is derived from the black-legged tick, an important vector of human and animal pathogens. We find abundant classes of ~22nt sRNAs that require specific combinations of RdRPs and sRNA effector proteins (Argonautes or AGOs). RdRP1-dependent sRNAs possess 5'-monophosphates and are mainly derived from RNA polymerase III-transcribed genes and repetitive elements. Knockdown of some RdRP homologs misregulates genes including RNAi-related genes and the regulator of immune response Dsor1. Sensor assays demonstrate that Dsor1 is downregulated by RdRP1 through the 3'UTR that contains a target site of RdRP1-dependent repeat-derived sRNAs. Consistent with viral gene repression by the RNAi mechanism using virus-derived small interfering RNAs, viral transcripts are upregulated by AGO knockdown. On the other hand, RdRP1 knockdown unexpectedly results in downregulation of viral transcripts. This effect is dependent on Dsor1, suggesting that antiviral immunity is enhanced by RdRP1 knockdown through Dsor1 upregulation. We propose that tick sRNA pathways control multiple aspects of immune response via RNAi and regulation of signaling pathways. National Research Foundation (NRF) Published version Research in K.O.’s group was supported by the National Research Foundation, Prime Minister’s Office, Singapore under its NRF Fellowship Programme (NRF2011NRF-NRFF001- 042), Temasek Life Sciences Laboratory core funding and the JSPS Fund for the Promotion of Joint International Research (Returning Researcher Development Research, 17K20145). Work in the T. T.’s group was supported by Takeda Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of these agencies. There was no additional external funding received for this study. 2023-08-01T02:27:19Z 2023-08-01T02:27:19Z 2023 Journal Article Feng, C., Torimaru, K., Lim, M. Y. T., Chak, L., Shiimori, M., Tsuji, K., Tanaka, T., Iida, J. & Okamura, K. (2023). A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick. PloS One, 18(3), e0281195-. https://dx.doi.org/10.1371/journal.pone.0281195 1932-6203 https://hdl.handle.net/10356/169716 10.1371/journal.pone.0281195 36996253 2-s2.0-85151316229 3 18 e0281195 en NRF2011NRF-NRFF001-042 17K20145 PloS one © 2023 Feng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Small Interfering RNA
Eukaryote
spellingShingle Science::Biological sciences
Small Interfering RNA
Eukaryote
Feng, Canran
Torimaru, Kyosuke
Lim, Mandy Yu Theng
Chak, Li-Ling
Shiimori, Masami
Tsuji, Kosuke
Tanaka, Tetsuya
Iida, Junko
Okamura, Katsutomo
A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
description Small regulatory RNAs (sRNAs) are involved in antiviral defense and gene regulation. Although roles of RNA-dependent RNA Polymerases (RdRPs) in sRNA biology are extensively studied in nematodes, plants and fungi, understanding of RdRP homologs in other animals is still lacking. Here, we study sRNAs in the ISE6 cell line, which is derived from the black-legged tick, an important vector of human and animal pathogens. We find abundant classes of ~22nt sRNAs that require specific combinations of RdRPs and sRNA effector proteins (Argonautes or AGOs). RdRP1-dependent sRNAs possess 5'-monophosphates and are mainly derived from RNA polymerase III-transcribed genes and repetitive elements. Knockdown of some RdRP homologs misregulates genes including RNAi-related genes and the regulator of immune response Dsor1. Sensor assays demonstrate that Dsor1 is downregulated by RdRP1 through the 3'UTR that contains a target site of RdRP1-dependent repeat-derived sRNAs. Consistent with viral gene repression by the RNAi mechanism using virus-derived small interfering RNAs, viral transcripts are upregulated by AGO knockdown. On the other hand, RdRP1 knockdown unexpectedly results in downregulation of viral transcripts. This effect is dependent on Dsor1, suggesting that antiviral immunity is enhanced by RdRP1 knockdown through Dsor1 upregulation. We propose that tick sRNA pathways control multiple aspects of immune response via RNAi and regulation of signaling pathways.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Feng, Canran
Torimaru, Kyosuke
Lim, Mandy Yu Theng
Chak, Li-Ling
Shiimori, Masami
Tsuji, Kosuke
Tanaka, Tetsuya
Iida, Junko
Okamura, Katsutomo
format Article
author Feng, Canran
Torimaru, Kyosuke
Lim, Mandy Yu Theng
Chak, Li-Ling
Shiimori, Masami
Tsuji, Kosuke
Tanaka, Tetsuya
Iida, Junko
Okamura, Katsutomo
author_sort Feng, Canran
title A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
title_short A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
title_full A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
title_fullStr A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
title_full_unstemmed A novel eukaryotic RdRP-dependent small RNA pathway represses antiviral immunity by controlling an ERK pathway component in the black-legged tick
title_sort novel eukaryotic rdrp-dependent small rna pathway represses antiviral immunity by controlling an erk pathway component in the black-legged tick
publishDate 2023
url https://hdl.handle.net/10356/169716
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