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Ding Group

Ding Group
Ding Group
Yiliang Ding
Honorary Group Leader
Ding Group

Yiliang is an Honorary Group Leader at the Institute and is group leader at the in Norwich where she is part of the Genes in the Environment research programme. In her affiliation with the Babraham Institute, Yiliang is working primarily with members of the Immunology programme. Yiliang’s research investigates the role of RNA structure in gene regulation, such as translation, spicing and degradation, with a focus on understanding the dynamics of RNA structure in living cells. The group’s approach involves developing new experimental and analytical methods for revealing RNA structure and RNA-protein interactions.

RNA molecules participate in every step of post-transcriptional regulation of gene expression. RNA folding is an intrinsic property that impacts the whole post-transcriptional processes from RNA splicing, polyadenylation, and translation, through to RNA degradation. Yiliang’s research focuses on the study of in vivo RNA structure functionalities across different RNA biological processes. Her research has developed several novel and advanced methods for studying in vivo RNA structure and has uncovered in vivo RNA structure functionalities in mRNA processing, translation and RNA degradation, demonstrating RNA structure to be a key regulator of gene expression.

Yiliang’s group has also developed novel technologies to reveal the existence of tertiary RNA G-quadruplex structures in eukaryotes and uncovered that RNA G-quadruplex structure serves as a molecular marker to facilitate stress response. For the first time, Yiliang’s group also discovered the RNA structure-triggered RNA-driven phase separation that was specifically associated with cell identity. Yiliang’s group has also established the single-molecule RNA structure profiling technology that revealed the functional role of RNA structure on one of long non-coding RNAs, COOLAIRs. Both knowledge and technology advances have transformed our understanding of gene regulation and promoted a new concept of exploiting RNA structure-guided molecular design in potential RNA therapeutics and crop improvement applications.

Latest Publications

Open Access
Yang X, Yu H, Duncan S, Zhang Y, Cheema J, Liu H, Benjamin Miller J, Zhang J, Kwok CK, Zhang H, Ding Y Immunology

Nucleotide composition is suggested to infer gene functionality and ecological adaptation of species to distinct environments. However, the underlying biological function of nucleotide composition dictating environmental adaptations is largely unknown. Here, we systematically analyze the nucleotide composition of transcriptomes across 1000 plants (1KP) and their corresponding habitats. Intriguingly, we find that plants growing in cold climates have guanine (G)-enriched transcriptomes, which are prone to forming RNA G-quadruplex structures. Both immunofluorescence detection and in vivo structure profiling reveal that RNA G-quadruplex formation in plants is globally enhanced in response to cold. Cold-responsive RNA G-quadruplexes strongly enhanced mRNA stability, rather than affecting translation. Disruption of individual RNA G-quadruplex promotes mRNA decay in the cold, leading to impaired plant cold response. Therefore, we propose that plants adopted RNA G-quadruplex structure as a molecular signature to facilitate their adaptation to the cold during evolution.

+view abstract Nature communications, PMID: 36266343

Open Access
Yu H, Qi Y, Yang B, Yang X, Ding Y Immunology

RNA G-quadruplex (rG4) is a vital RNA tertiary structure motif that involves the base pairs on both Hoogsteen and Watson-Crick faces of guanines. rG4 is of great importance in the post-transcriptional regulation of gene expression. Experimental technologies have advanced to identify in vitro and in vivo rG4s across diverse transcriptomes. Building on these recent advances, here we present G4Atlas, the first transcriptome-wide G-quadruplex database, in which we have collated, classified, and visualized transcriptome rG4 experimental data, generated from rG4-seq, chemical profiling and ligand-binding methods. Our comprehensive database includes transcriptome-wide rG4s generated from 82 experimental treatments and 238 samples across ten species. In addition, we have also included RNA secondary structure prediction information across both experimentally identified and unidentified rG4s to enable users to display any potential competitive folding between rG4 and RNA secondary structures. As such, G4Atlas will enable users to explore the general functions of rG4s in diverse biological processes. In addition, G4Atlas lays the foundation for further data-driven deep learning algorithms to examine rG4 structural features.

+view abstract Nucleic acids research, PMID: 36243987

Open Access
Yang M, Zhu P, Cheema J, Bloomer R, Mikulski P, Liu Q, Zhang Y, Dean C, Ding Y Immunology

Cellular RNAs are heterogeneous with respect to their alternative processing and secondary structures, but the functional importance of this complexity is still poorly understood. A set of alternatively processed antisense non-coding transcripts, which are collectively called COOLAIR, are generated at the Arabidopsis floral-repressor locus FLOWERING LOCUS C (FLC). Different isoforms of COOLAIR influence FLC transcriptional output in warm and cold conditions. Here, to further investigate the function of COOLAIR, we developed an RNA structure-profiling method to determine the in vivo structure of single RNA molecules rather than the RNA population average. This revealed that individual isoforms of the COOLAIR transcript adopt multiple structures with different conformational dynamics. The major distally polyadenylated COOLAIR isoform in warm conditions adopts three predominant structural conformations, the proportions and conformations of which change after cold exposure. An alternatively spliced, strongly cold-upregulated distal COOLAIR isoform shows high structural diversity, in contrast to proximally polyadenylated COOLAIR. A hyper-variable COOLAIR structural element was identified that was complementary to the FLC transcription start site. Mutations altering the structure of this region changed FLC expression and flowering time, consistent with an important regulatory role of the COOLAIR structure in FLC transcription. Our work demonstrates that isoforms of non-coding RNA transcripts adopt multiple distinct and functionally relevant structural conformations, which change in abundance and shape in response to external conditions.

+view abstract Nature, PMID: 35978193

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Group Members

Yiliang Ding

Honorary Group Leader