m⁶A modifications of nascent FLC inhibit its transcription by preventing H3K36me3 modification

Y. L. SHAO, H. YU.

Temasek Life Sciences Laboratory, National University of Singapore, 1 Research Link, 117604, Singapore

RNA modifications constitute an essential layer of gene regulation in living organisms. However, the molecular basis of m⁶A modification is largely unknown in plants. Here, we show that MBIP1, a zinc-finger protein, is an essential component of the m⁶A methyltransferase complex in Arabidopsis. Depletion of MBIP1 decreased global MTA and MTB protein contents, but did not alter the subcellular localization of MTA and MTB. The mutants lacking MBIP1 exhibited late flowering associated with a decreased m⁶A modification on nascent RNA, which in turn activated nascent RNA transcription. Further analysis showed that m⁶A modification of nascent FLC decreased in the mbip1-1 mutant. Decreased m⁶A modification of nascent FLC promoted transcriptional initiation and elongation of FLC, resulting in later flowering. Furthermore, we found that MBIP1 interacted with SDG8, an H3K36me3 methyltransferase. The interaction between MBIP1 and SDG8 prevented H3K36me3 deposition at the FLC locus. Collectively, our studies reveal an important role of nascent RNA methylation in affecting gene transcription, and uncover another layer of gene expression regulation that involves crosstalk between nascent RNA methylation and histone modification.