Epitranscriptomic turbo for autophagy boost: m6A reader YTHDF3

WeiChao Hao; MeiJuan Dian; JiaHong Wang; Yan Sun; Dong Xiao

doi:10.1080/15548627.2022.2146890

Epitranscriptomic turbo for autophagy boost: m⁶A reader YTHDF3

Autophagy. 2023 Jun;19(6):1882-1884. doi: 10.1080/15548627.2022.2146890. Epub 2022 Nov 29.

Authors

WeiChao Hao^{1

2}, MeiJuan Dian^{3

4}, JiaHong Wang², Yan Sun⁵, Dong Xiao^{2

4}

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
² Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
³ Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁴ Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
⁵ Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Abstract

Mcroautophagy/autophagy plays an important role in maintaining homeostasis during nutrient starvation. However, whether epitranscriptomic events are involved in this process remains unclear. Our recent findings suggest that m⁶A reader YTHDF3 has an essential role in autophagy induction. Elevated m⁶A modifications installed by METTL3 enable YTHDF3 to promote autophagosome formation and lysosomal function upon nutrient deficiency. This is due to YTHDF3 binding to the m⁶A modifications at the coding DNA sequence (CDS) and 3' untranslated region (UTR) around the stop codon of Foxo3 mRNA, recruiting EIF3A and EIF4B to facilitate FOXO3 translation, thus boosting autophagy. In this punctum, we discuss our finding for how YTHDF3 responds to nutrient starvation to promote autophagy flux, providing insights into RNA post-transcriptional modifications linking nutrient cues to autophagic upcycling.

Keywords: Autophagy; FOXO3; METTL3; YTHDF3; epitranscriptomics; m6A; nutrient starvation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy* / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism

Substances

RNA, Messenger

Grants and funding

This work is funded by the National Natural Science Foundation of China (81872209, 82173299, 81672689, 81372896, 81172587, 81600086, 81770100), Natural Science Foundation of Guangdong Province of China (2022A1515012477, 2014A030313294), Science and Technology Planning Project of Guangdong Province of China (2017A010105017, 2013B060300013, 2009B060300008), Medical Scientific Research Foundation of Guangdong Province of China (A2022107, B2020010), Guangzhou Basic and Applied Basic Research Foundation (202201010139, 202102020697).