NAD capping of RNAs: mechanisms and functions
Project Description
Gene expression is the process by which a gene (DNA) is converted into a functional product, such as a protein. Messenger RNAs (mRNAs) act as the intermediates in gene expression and carry the instructions for making proteins from genes. Proper regulation of gene expression, encompassing transcriptional and translational processes, is crucial for normal growth, development, and environmental adaptation. Cells modify mRNAs in different ways to mediate their functions. Eukaryotic mRNAs typically feature a m7G cap at their 5’ end, playing pivotal roles throughout gene expression. Recently, it has been reported that RNAs in various organisms carry alternative caps, such as the NAD cap. These findings indicate a novel mechanism in regulating gene expression through NAD capping.
This project focuses on unravelling the mechanism and function of NAD capping. We have developed multiple methods for identifying and characterising NAD capped-RNAs (NAD-RNAs). intriguing features of NAD-RNAs across various organisms and their potential functions have been unveiled. Our investigations suggest an interconnection between NAD capping/decapping and the canonical m7G capping process in regulating transcription in Arabidopsis and its possible function in influencing gene expression. Moreover, we found significantly heightened levels of certain NAD-RNAs in cancer cells compared to normal cells, hinting at a potential role in tumorigenesis. These findings represent significant progress in our project, paving the way for further exploration to uncover novel mechanisms governing gene expression through NAD capping in various critical biological processes.
Project Investigator
Professor XIA Yiji (Department of Biology)
Project Collaborators
- Professor CAI Zongwei (Department of Chemistry)
- Professor AIK Wei Shen (Department of Chemistry)
- Professor XIONG Liming (Department of Biology)
- The Chinese University of Hong Kong
- City University of Hong Kong
Funding/ Award
- Research Grants Council - General Research Fund
- Research Grants Council - Collaborative Research Fund
- National Natural Science Foundation of China & Research Grants Council - National Natural Science Foundation of China/RGC Collaborative Research Scheme
Publications
- Chen Xiao, Kaien Li, Jingmin Hua, Zhao He, Qiongfang Li, Hailei Zhang, Lei Yang, Shuying Pan, Zongwei Cai, Zhiling Yu, Kam-Bo Wong, Y Xia* (2023) Arabidopsis DXO1 activates RNMT1 to methylate the mRNA guanosine cap. Nature Communications, https://doi.org/10.1038/s41467-023-35903-8.
- 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. https://doi.org/10.1073/pnas.2026183118.
- H Hu, N Flynn, H Zhang, C You, R Hang, X Wang, H Zhong, Z Chan, Y Xia*, and X Chen (2021) SPAAC-NAD-seq, a sensitive and accurate method to profile NAD+-capped transcripts. Proc Natl Acad Sci USA, 118 (13) e2025595118. https://doi.org/10.1073/pnas.2025595118
- H Hu, N Flynn, H Zhang, C You, R Hang, X Wang, H Zhong, Z Chan, Y Xia*, and X Chen (2021) SPAAC-NAD-seq, a sensitive and accurate method to profile NAD+-capped transcripts. Proc Natl Acad Sci USA, 118 (13) e2025595118. https://doi.org/10.1073/pnas.202559511
- 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, 116 (24) 12072-12077, https://doi.org/10.1073/pnas.1903683116.
- Wang Y, Li S, Zhao Y, You C, Le B, Gong Z, Mo B, Xia Y, Chen X (2019) NAD+-capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated. Proc Natl Acad Sci USA, 116(24):12094-12102, https://doi.org/10.1073/pnas.190368211
