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5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes
5-methylcytosine (m(5)C) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if m(5)C modification contributes to the dynamic regulation of the transcriptome during the devel...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892369/ https://www.ncbi.nlm.nih.gov/pubmed/35210361 http://dx.doi.org/10.1073/pnas.2110713119 |
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author | Liu, Meng Guo, Gangqiang Qian, Pengge Mu, Jianbing Lu, Binbin He, Xiaoqin Fan, Yanting Shang, Xiaomin Yang, Guang Shen, Shijun Liu, Wenju Wang, Liping Gu, Liang Mu, Quankai Yu, Xinyu Zhao, Yuemeng Culleton, Richard Cao, Jun Jiang, Lubin Wellems, Thomas E. Yuan, Jing Jiang, Cizhong Zhang, Qingfeng |
author_facet | Liu, Meng Guo, Gangqiang Qian, Pengge Mu, Jianbing Lu, Binbin He, Xiaoqin Fan, Yanting Shang, Xiaomin Yang, Guang Shen, Shijun Liu, Wenju Wang, Liping Gu, Liang Mu, Quankai Yu, Xinyu Zhao, Yuemeng Culleton, Richard Cao, Jun Jiang, Lubin Wellems, Thomas E. Yuan, Jing Jiang, Cizhong Zhang, Qingfeng |
author_sort | Liu, Meng |
collection | PubMed |
description | 5-methylcytosine (m(5)C) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if m(5)C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m(5)C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (Plasmodium yoelii) and human (Plasmodium falciparum) malaria parasites. While different representations of m(5)C-modified mRNAs are associated with the different stages, the abundance of the m(5)C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m(5)C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m(5)C methyltransferase in malaria parasites. Upon knockout of P. yoelii nsun2 (pynsun2), marked reductions of m(5)C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the nsun2 gene in the knockout parasites rescued the gametocyte production phenotype as well as m(5)C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m(5)C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m(5)C modifications in mRNA transcript stability and sexual differentiation in malaria parasites. |
format | Online Article Text |
id | pubmed-8892369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-88923692022-08-24 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes Liu, Meng Guo, Gangqiang Qian, Pengge Mu, Jianbing Lu, Binbin He, Xiaoqin Fan, Yanting Shang, Xiaomin Yang, Guang Shen, Shijun Liu, Wenju Wang, Liping Gu, Liang Mu, Quankai Yu, Xinyu Zhao, Yuemeng Culleton, Richard Cao, Jun Jiang, Lubin Wellems, Thomas E. Yuan, Jing Jiang, Cizhong Zhang, Qingfeng Proc Natl Acad Sci U S A Biological Sciences 5-methylcytosine (m(5)C) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if m(5)C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m(5)C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (Plasmodium yoelii) and human (Plasmodium falciparum) malaria parasites. While different representations of m(5)C-modified mRNAs are associated with the different stages, the abundance of the m(5)C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m(5)C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m(5)C methyltransferase in malaria parasites. Upon knockout of P. yoelii nsun2 (pynsun2), marked reductions of m(5)C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the nsun2 gene in the knockout parasites rescued the gametocyte production phenotype as well as m(5)C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m(5)C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m(5)C modifications in mRNA transcript stability and sexual differentiation in malaria parasites. National Academy of Sciences 2022-02-24 2022-03-01 /pmc/articles/PMC8892369/ /pubmed/35210361 http://dx.doi.org/10.1073/pnas.2110713119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Liu, Meng Guo, Gangqiang Qian, Pengge Mu, Jianbing Lu, Binbin He, Xiaoqin Fan, Yanting Shang, Xiaomin Yang, Guang Shen, Shijun Liu, Wenju Wang, Liping Gu, Liang Mu, Quankai Yu, Xinyu Zhao, Yuemeng Culleton, Richard Cao, Jun Jiang, Lubin Wellems, Thomas E. Yuan, Jing Jiang, Cizhong Zhang, Qingfeng 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes |
title | 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes |
title_full | 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes |
title_fullStr | 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes |
title_full_unstemmed | 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes |
title_short | 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes |
title_sort | 5-methylcytosine modification by plasmodium nsun2 stabilizes mrna and mediates the development of gametocytes |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892369/ https://www.ncbi.nlm.nih.gov/pubmed/35210361 http://dx.doi.org/10.1073/pnas.2110713119 |
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