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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
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.
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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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