Two zinc finger proteins with functions in m6A writing interact with HAKAI

Abstract

The methyltransferase complex (m6A writer), which catalyzes the deposition of N6-methyladenosine (m6A) in mRNAs, is highly conserved across most eukaryotic organisms, but its components and interactions between them are still far from fully understood. Here, using in vivo interaction proteomics, two HAKAI-interacting zinc finger proteins, HIZ1 and HIZ2, are discovered as components of the Arabidopsis m6A writer complex. HAKAI is required for the interaction between HIZ1 and MTA (mRNA adenosine methylase A). Whilst HIZ1 knockout plants have normal levels of m6A, plants in which it is overexpressed show reduced methylation and decreased lateral root formation. Mutant plants lacking HIZ2 are viable but have an 85% reduction in m6A abundance and show severe developmental defects. Our findings suggest that HIZ2 is likely the plant equivalent of ZC3H13 (Flacc) of the metazoan m6A-METTL Associated Complex.

Zinc in Cognitive Impairment and Aging

“…YTHDF3 enhances the stability of ZEB1 mRNA in an m6A-dependent manner and positively regulates cell migration, invasion, and the EMT [ 236 ]. Arabidopsis HAKAI is necessary for complete m6A methylation, and its knockout leads to a 35% reduction in m6A abundance [ 237 ]. ZFPs 1 and 2 (HIZ1 and HIZ2) interact with HAKAI and are members of the m6A writer complex.…”

The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer

“…The METTL3-METTL14 heterodimer interacts with additional proteins, including Wilms tumour 1-associated protein (WTAP), RNA-binding motif protein 15 (RBM15), RBM15B, vir-Like m6A methyltransferase associated (VIRMA, also known as KIAA1429), and Zinc Finger CCCH-Type Containing 13 (ZC3H13), all of which are required for m6A methylation [ 6 , 8 , 10 , 11 , 12 , 13 ]. Moreover, other proteins including the E3 ubiquitin-protein ligase Hakai (HAKAI) and associated proteins, are required for the full methylation ability in Arabidopsis [ 14 , 15 ]. Studies also suggest that the mammalian HAKAI homologue, cbl protooncogene like 1 (CBLL1), is also involved in the mammalian m6A methyltransferase complex [ 16 ].…”

The RNA N6‐methyladenosine demethylase ALKBH9B modulates ABA responses in Arabidopsis

“…The reversible methylation of m 6 A is catalyzed, removed, and recognized by methyltransferases (writers), demethylases (erasers), and m 6 A binding proteins (readers), respectively. In Arabidopsis ( Arabidopsis thaliana ), two types of mRNA m 6 A methyltransferase have been identified: a multi‐protein complex comprising MRNA ADENOSINE METHYLASE (MTA), METHYLTRANSFERASE B (MTB), FKBP12 INTERACTING PROTEIN 37 (FIP37), VIRILIZER (VIR), HAKAI, and HAKAI‐INTERACTING ZINC FINGER PROTEIN 2 (HIZ2) (Zhong et al, 2008; Shen et al, 2016; Ruzicka et al, 2017; Zhang et al, 2022) and FIONA1 (FIO1), a homolog of mammalian Methyltransferase‐like 16 (METTL16) (Wang et al, 2022; Xu et al, 2022). Two m 6 A demethylases (ALKBH9B and ALKBH10B) and several m 6 A readers (EVOLUTIONARILY CONSERVED C‐TERMINAL REGION 2 [ECT2], ECT3, ECT4, and CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR 30 [CPSF30‐L]) have been identified in Arabidopsis (Duan et al, 2017; Martinez‐Perez et al, 2017; Arribas‐Hernandez et al, 2018; Scutenaire et al, 2018; Wei et al, 2018; Hou et al, 2021; Song et al, 2021).…”

“…Two m 6 A demethylases (ALKBH9B and ALKBH10B) and several m 6 A readers (EVOLUTIONARILY CONSERVED C‐TERMINAL REGION 2 [ECT2], ECT3, ECT4, and CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR 30 [CPSF30‐L]) have been identified in Arabidopsis (Duan et al, 2017; Martinez‐Perez et al, 2017; Arribas‐Hernandez et al, 2018; Scutenaire et al, 2018; Wei et al, 2018; Hou et al, 2021; Song et al, 2021). The RNA m 6 A modification has been shown to play vital roles in plant development (Arribas‐Hernandez and Brodersen, 2020; Liang et al, 2020; Wang et al, 2021; Cheng et al, 2022; Wang et al, 2022; Zhang et al, 2022) and biotic (Martinez‐Perez et al, 2017; Guo et al, 2021; Ren et al, 2022) and abiotic stress responses (Hu et al, 2021; Tang et al, 2021; Hou et al, 2022), and it also contributes to the improvement of crop traits (Yu et al, 2021).…”