Knockdown of METTL16 disrupts learning and memory by reducing the stability of MAT2A mRNA

Runjiao Zhang; Yizhou Zhang; Fangzhen Guo; Guannan Huang; Yan Zhao; Bingyu Chen; Chang Wang; Chengran Cui; Yichun Shi; Sha Li; Huixian Cui

doi:10.1038/s41420-022-01220-0

Knockdown of METTL16 disrupts learning and memory by reducing the stability of MAT2A mRNA

Cell Death Discov. 2022 Oct 28;8(1):432. doi: 10.1038/s41420-022-01220-0.

Authors

Runjiao Zhang^#^{1

2}, Yizhou Zhang^#^{1

2

3}, Fangzhen Guo^{1

2}, Guannan Huang⁴, Yan Zhao^{1

2

5}, Bingyu Chen^{1

2}, Chang Wang^{1

2

3}, Chengran Cui⁶, Yichun Shi⁶, Sha Li^{7

8

9}, Huixian Cui^{10

11

12}

Affiliations

¹ Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
² Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
³ Hebei Key Laboratory of Neurodegenerative Disease Mechanism, 050017, Shijiazhuang, Hebei, China.
⁴ Department of Ultrasound, The Second Hospital of Hebei Medical University, 050000, Shijiazhuang, Hebei, China.
⁵ School of Nursing, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
⁶ Grade 2019, Basic Medicine, Hebei Medical University, 050017, Shijiazhuang, Hebei, China.
⁷ Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. lisha@hebmu.edu.cn.
⁸ Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. lisha@hebmu.edu.cn.
⁹ Hebei Key Laboratory of Neurodegenerative Disease Mechanism, 050017, Shijiazhuang, Hebei, China. lisha@hebmu.edu.cn.
¹⁰ Department of Anatomy, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. cuihx@hebmu.edu.com.
¹¹ Neuroscience Research Center, Hebei Medical University, 050017, Shijiazhuang, Hebei, China. cuihx@hebmu.edu.com.
¹² Hebei Key Laboratory of Neurodegenerative Disease Mechanism, 050017, Shijiazhuang, Hebei, China. cuihx@hebmu.edu.com.

^# Contributed equally.

Abstract

N6-methyladenosine (m⁶A) is abundant in the mammalian brain and is considered to have a wide range of effects on learning and memory. Here, we found that the upregulated methyltransferase-like protein 16 (METTL16) in the hippocampal tissues of Morris water maze (MWM)-trained mice contributed to improved memory formation and hippocampal synaptic plasticity. Mechanismly, METTL16 promoted the expression of methionine adenosyltransferase 2A (MAT2A) by the m⁶A methylation of the MAT2A mRNA-3'UTR-end to increase its stability, and this involved in improving hippocampal global m⁶A levels, plasticity of dendritic spine, learning and memory. This study provides a new perspective to explore the regulatory mechanisms of m⁶A for learning and memory.

Abstract

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