The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons

Abstract Messenger RNA m6A modification is shown to regulate local translation in axons. However, how the m6A codes in axonal mRNAs are read and decoded by the m6A reader proteins is still unknown. Here, it is found that the m6A readers YTHDF1 and YTHDF2 are both expressed in cerebellar granule cell...

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Autores principales:	Jun Yu, Yuanchu She, Lixin Yang, Mengru Zhuang, Peng Han, Jianhui Liu, Xiaoyan Lin, Nijia Wang, Mengxian Chen, Chunxuan Jiang, Yujia Zhang, Yujing Yuan, Sheng‐Jian Ji
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cerebellar parallel fibers local translation m6A YTHDF1 YTHDF2 Science Q
Acceso en línea:	https://doaj.org/article/29ce9c74894b42f3ab2f35e0c7393669
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spelling	oai:doaj.org-article:29ce9c74894b42f3ab2f35e0c73936692021-11-17T08:40:31ZThe m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons2198-384410.1002/advs.202101329https://doaj.org/article/29ce9c74894b42f3ab2f35e0c73936692021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202101329https://doaj.org/toc/2198-3844Abstract Messenger RNA m6A modification is shown to regulate local translation in axons. However, how the m6A codes in axonal mRNAs are read and decoded by the m6A reader proteins is still unknown. Here, it is found that the m6A readers YTHDF1 and YTHDF2 are both expressed in cerebellar granule cells (GCs) and their axons. Knockdown (KD) of YTHDF1 or YTHDF2 significantly increases GC axon growth rates in vitro. By integrating anti‐YTHDF1&2 RIP‐Seq with the quantitative proteomic analysis or RNA‐seq after KD of YTHDF1 or YTHDF2, a group of transcripts which may mediate the regulation of GC axon growth by YTHDFs is identified. Among them, Dvl1 and Wnt5a, encoding the key components of Wnt pathway, are further found to be locally translated in axons, which are controlled by YTHDF1 and YTHDF2, respectively. Specific ablation of Ythdf1 or Ythdf2 in GCs increases parallel fiber growth, promotes synapse formation in cerebellum in vivo, and improves motor coordination ability. Together, this study identifies a mechanism by which the m6A readers YTHDF1 and YTHDF2 work synergistically on the Wnt5a pathway through regulating local translation in GC axons to control cerebellar parallel fiber development.Jun YuYuanchu SheLixin YangMengru ZhuangPeng HanJianhui LiuXiaoyan LinNijia WangMengxian ChenChunxuan JiangYujia ZhangYujing YuanSheng‐Jian JiWileyarticlecerebellar parallel fiberslocal translationm6AYTHDF1YTHDF2ScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cerebellar parallel fibers local translation m6A YTHDF1 YTHDF2 Science Q
spellingShingle	cerebellar parallel fibers local translation m6A YTHDF1 YTHDF2 Science Q Jun Yu Yuanchu She Lixin Yang Mengru Zhuang Peng Han Jianhui Liu Xiaoyan Lin Nijia Wang Mengxian Chen Chunxuan Jiang Yujia Zhang Yujing Yuan Sheng‐Jian Ji The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons
description	Abstract Messenger RNA m6A modification is shown to regulate local translation in axons. However, how the m6A codes in axonal mRNAs are read and decoded by the m6A reader proteins is still unknown. Here, it is found that the m6A readers YTHDF1 and YTHDF2 are both expressed in cerebellar granule cells (GCs) and their axons. Knockdown (KD) of YTHDF1 or YTHDF2 significantly increases GC axon growth rates in vitro. By integrating anti‐YTHDF1&2 RIP‐Seq with the quantitative proteomic analysis or RNA‐seq after KD of YTHDF1 or YTHDF2, a group of transcripts which may mediate the regulation of GC axon growth by YTHDFs is identified. Among them, Dvl1 and Wnt5a, encoding the key components of Wnt pathway, are further found to be locally translated in axons, which are controlled by YTHDF1 and YTHDF2, respectively. Specific ablation of Ythdf1 or Ythdf2 in GCs increases parallel fiber growth, promotes synapse formation in cerebellum in vivo, and improves motor coordination ability. Together, this study identifies a mechanism by which the m6A readers YTHDF1 and YTHDF2 work synergistically on the Wnt5a pathway through regulating local translation in GC axons to control cerebellar parallel fiber development.
format	article
author	Jun Yu Yuanchu She Lixin Yang Mengru Zhuang Peng Han Jianhui Liu Xiaoyan Lin Nijia Wang Mengxian Chen Chunxuan Jiang Yujia Zhang Yujing Yuan Sheng‐Jian Ji
author_facet	Jun Yu Yuanchu She Lixin Yang Mengru Zhuang Peng Han Jianhui Liu Xiaoyan Lin Nijia Wang Mengxian Chen Chunxuan Jiang Yujia Zhang Yujing Yuan Sheng‐Jian Ji
author_sort	Jun Yu
title	The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons
title_short	The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons
title_full	The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons
title_fullStr	The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons
title_full_unstemmed	The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons
title_sort	m6a readers ythdf1 and ythdf2 synergistically control cerebellar parallel fiber growth by regulating local translation of the key wnt5a signaling components in axons
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/29ce9c74894b42f3ab2f35e0c7393669
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The m6A Readers YTHDF1 and YTHDF2 Synergistically Control Cerebellar Parallel Fiber Growth by Regulating Local Translation of the Key Wnt5a Signaling Components in Axons

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