Most cited article - PubMed ID 28503769
Identification of factors required for m6 A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI
N6-methyladenosine (m6A) modification of mRNAs affects many biological processes. However, the function of m6A in plant photosynthesis remains unknown. Here, we demonstrate that m6A modification is crucial for photosynthesis during photodamage caused by high light stress in plants. The m6A modification levels of numerous photosynthesis-related transcripts are changed after high light stress. We determine that the Arabidopsis m6A writer VIRILIZER (VIR) positively regulates photosynthesis, as its genetic inactivation drastically lowers photosynthetic activity and photosystem protein abundance under high light conditions. The m6A levels of numerous photosynthesis-related transcripts decrease in vir mutants, extensively reducing their transcript and translation levels, as revealed by multi-omics analyses. We demonstrate that VIR associates with the transcripts of genes encoding proteins with functions related to photoprotection (such as HHL1, MPH1, and STN8) and their regulatory proteins (such as regulators of transcript stability and translation), promoting their m6A modification and maintaining their stability and translation efficiency. This study thus reveals an important mechanism for m6A-dependent maintenance of photosynthetic efficiency in plants under high light stress conditions.
- MeSH
- Arabidopsis * genetics MeSH
- Photosynthesis * genetics MeSH
- RNA, Messenger genetics MeSH
- Gene Silencing MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- RNA, Messenger MeSH
- N-methyladenosine MeSH Browser
N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.
- MeSH
- Adaptor Proteins, Signal Transducing genetics metabolism MeSH
- Adenosine analogs & derivatives metabolism MeSH
- AlkB Homolog 5, RNA Demethylase genetics metabolism MeSH
- Molecular Sequence Annotation MeSH
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics metabolism MeSH
- Transcription, Genetic MeSH
- Gene Ontology MeSH
- HEK293 Cells MeSH
- Nuclear Proteins genetics metabolism MeSH
- Humans MeSH
- Protein Interaction Mapping MeSH
- RNA, Messenger genetics metabolism MeSH
- Methyltransferases genetics metabolism MeSH
- Oxidoreductases, N-Demethylating genetics metabolism MeSH
- RNA, Untranslated genetics metabolism MeSH
- DNA Repair MeSH
- Protein Isoforms genetics metabolism MeSH
- DNA Replication MeSH
- Protein Binding MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing MeSH
- Adenosine MeSH
- AlkB Homolog 5, RNA Demethylase MeSH
- ALKBH5 protein, human MeSH Browser
- FTO protein, human MeSH Browser
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Nuclear Proteins MeSH
- RNA, Messenger MeSH
- Methyltransferases MeSH
- METTL16 protein, human MeSH Browser
- Oxidoreductases, N-Demethylating MeSH
- N-methyladenosine MeSH Browser
- N(6),N(6)-dimethyladenosine MeSH Browser
- RNA, Untranslated MeSH
- PCIF1 protein, human MeSH Browser
- Protein Isoforms MeSH
Eukaryotic RNA can carry more than 100 different types of chemical modifications. Early studies have been focused on modifications of highly abundant RNA, such as ribosomal RNA and transfer RNA, but recent technical advances have made it possible to also study messenger RNA (mRNA). Subsequently, mRNA modifications, namely methylation, have emerged as key players in eukaryotic gene expression regulation. The most abundant and widely studied internal mRNA modification is N6 -methyladenosine (m6 A), but the list of mRNA chemical modifications continues to grow as fast as interest in this field. Over the past decade, transcriptome-wide studies combined with advanced biochemistry and the discovery of methylation writers, readers, and erasers revealed roles for mRNA methylation in the regulation of nearly every aspect of the mRNA life cycle and in diverse cellular, developmental, and disease processes. Although large parts of mRNA function are linked to its cytoplasmic stability and regulation of its translation, a number of studies have begun to provide evidence for methylation-regulated nuclear processes. In this review, we summarize the recent advances in RNA methylation research and highlight how these new findings have contributed to our understanding of methylation-dependent RNA processing in the nucleus. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Processing > Splicing Regulation/Alternative Splicing RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
- Keywords
- RNA demethylase, RNA methylase, RNA processing,
- MeSH
- Cell Nucleus metabolism MeSH
- Epigenesis, Genetic MeSH
- Humans MeSH
- RNA, Messenger metabolism MeSH
- Methylation MeSH
- RNA Precursors metabolism MeSH
- Transcriptome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- RNA, Messenger MeSH
- RNA Precursors MeSH