bims-nocaut 2022-08-21 papers

Issue of 2022‒08‒21
two papers selected by
Quentin Frenger
University of Strasbourg

Autophagy. 2022 Aug 13. 1-3

The role of LC3B in autophagy as an RNA-binding protein.

The hallmark of cellular events observed upon macroautophagic/autophagic induction is the conjugation of LC3B, one of the mammalian Atg8 homologs, with phosphatidylethanolamine. This conversion from LC3B-I (an unconjugated form) to LC3B-II (a conjugated form) is essential for phagophore expansion and formation of autophagosomes. Our recent study revealed that LC3B binds to RNAs with a preference for the consensus AAUAAA motif and recruits the CCR4-NOT deadenylase complex. Consequently, LC3B elicits rapid degradation of mRNAs, which we have termed as LC3B-mediated mRNA decay (LMD). LMD requires the conversion of LC3B-I to LC3B-II and occurs before the formation of autolysosomes. Furthermore, we identified PRMT1 mRNA, which encodes a protein that functions as a negative regulator of autophagy, as an LMD substrate. A failure of rapid degradation of PRMT1 mRNA via LMD results in inefficient autophagy. Thus, our study unravels an important role of LC3B in autophagy as an RNA-binding protein for efficient mRNA decay.

Keywords: ATG8; CCR4-NOT deadenylase; LC3B; PRMT1; autophagy; mRNA decay

DOI: https://doi.org/10.1080/15548627.2022.2111083

Cell Rep. 2022 Aug 16. pii: S2211-1247(22)01012-9. [Epub ahead of print]40(7): 111195

Nondegradable ubiquitinated ATG9A organizes Golgi integrity and dynamics upon stresses.

Qian Luo, Qiangqiang Liu, Hongcheng Cheng, Jiale Wang, Tian Zhao, Jiaojiao Zhang, Chenglong Mu, Yuanyuan Meng, Linbo Chen, Changqian Zhou, Hong Lei, Jianyu Yang, Guo Chen, Yanjun Li, Leiting Pan, Quan Chen, Yushan Zhu.

ATG9A is a highly conserved membrane protein required for autophagy initiation. It is trafficked from the trans-Golgi network (TGN) to the phagophore to act as a membrane source for autophagosome expansion. Here, we show that ATG9A is not just a passenger protein in the TGN but rather works in concert with GRASP55, a stacking factor for Golgi structure, to organize Golgi dynamics and integrity. Upon heat stress, the E3 ubiquitin ligase MARCH9 is promoted to ubiquitinate ATG9A in the form of K63 conjugation, and the nondegradable ubiquitinated ATG9A disperses from the Golgi apparatus to the cytoplasm more intensely, accompanied by inhibiting GRASP55 oligomerization, further resulting in Golgi fragmentation. Knockout of ATG9A or MARCH9 largely prevents Golgi fragmentation and protects Golgi functions under heat and other Golgi stresses. Our results reveal a noncanonical function of ATG9A for Golgi dynamics and suggest the pathway for sensing Golgi stress via the MARCH9/ATG9A axis.

Keywords: ATG9A; CP: Molecular biology; Golgi dynamics; Golgi stress response; ubiquitination

DOI: https://doi.org/10.1016/j.celrep.2022.111195