报告题目：NAD-capped RNAs: what are they and what do they do？（NAD-capped RNA及其功能）
工作单位：Department of Biology， Hong Kong Baptist University（香港浸会大学生物系）
联系人：陈旭君 副教授 62734962
Eukaryotic mRNA typically contains the 7-methylguanosine cap (the m7G cap), which not only protects mRNAs from degradation but also plays an essential role in other steps of RNA metabolism and function, such as pre-mRNA processing and translation initiation. m7G capping was once considered to be a constitutive housekeeping process; however, growing evidence indicates that it is dynamically regulated in response to stimuli. In recent years, some RNAs in both prokaryotes and eukaryotes were found to contain non-canonical caps, such as the NAD cap, indicating another layer of control of gene expression by RNA capping.
We have developed multiple methods for global-scale profiling of NAD-capped RNAs (NAD-RNAs). In those methods, NAD-RNAs are tagged by an enzymatic reaction and click chemistry. Labelled NAD-RNAs can then be enriched to make a library and identified by a 2nd or 3rd generation sequencing technology. Our recent data from NAD-RNA profiling of various organisms, including Arabidopsis and micro-organisms, will be presented.
In plants, we have found that the Arabidopsis NAD-RNA decapping enzyme DXO1 is also an essential component of m7G capping. DXO1 binds to and activate RNMT1 which methylates the guanosine cap of pre-mRNA to form the m7G cap. The finding indicates a novel mechanism in m7G capping in plants by coupling with decapping of NAD-RNA. Studies of the emerging NAD-RNA biology could elucidate novel mechanisms controlling important biological processes, such as organisms’ responses to environmental stimuli.
1. C Xiao, K Li, J Hua, Z He, Q Li, H Zhang, L Yang, S Pan, Z Cai, Z Yu, KB Wong, Y Xia (2023) Arabidopsis DXO1 activates RNMT1 to methylate the mRNA guanosine cap. Nature Communications, DOI: 10.1038/s41467-023-35903-8.
2. H Zhang, H Zhong, X Wang, S Zhang, X Shao, H Hu, Z Yu, Z Cai, X Chen and Y Xia (2021) Use of NAD tagSeq II to identify growth phase-dependent alterations in E. coli NAD-capping. Proc Natl Acad Sci USA, 118(14): e2026183118.
3. Zhang H, Zhong H, Zhang S, Shao X, Ni M, Cai Z, Chen X, Xia Y (2019) NAD tagSeq reveals that NAD+-capped RNAs are mostly produced from a large number of protein-coding genes in Arabidopsis. Proc Natl Acad Sci USA, doi:10.1073/pnas.1903683116.
夏亦荠，香港浸会大学生物系讲席教授。于1997年在美国爱荷华州立大学获得遗传学博士学位；2001-2009年担任美国圣路易斯Danforth植物科学中心的首席研究员；2009年加入香港浸会大学。目前研究重点是RNA加帽的分子机制及其在调节基因表达和逆境反应中的作用。除了经典的真核生物mRNA的m7G端帽，近几年在真核生物和原核生物的许多RNA中也发现了新的端帽，如NAD端帽。然而，NAD加帽的机制及其分子和生理功能还所知甚少。夏亦荠实验室近几年开发了识别与鉴定NAD-RNA的新方法，并使用分子生物学、遗传学、生物化学和功能基因组学等方法研究拟南芥、大肠杆菌、酵母和人类细胞中RNA加帽在基因调控中的作用机制。夏亦荠教授在Nature, PNAS, Nature Protocols, Nature Communications, Plant Cell, EMBO Journal, Nucleic Acids Research等期刊发表了60多篇研究论文，被引用次数超过8600次。