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Printable Handouts
Navigable Slide Index
- Introduction
- Dynamic RNA modifications in diseases
- RNA modification in gene expression regulation
- Pseudouridine (Ψ)
- Ψ detection via selective labeling
- CeU-Seq identifies 2,084 Ψ sites in 293T transcriptome
- Ψ is abundant in mammalian Mrna
- Pseudouridylation is inducible and displays stress-specific pattern
- Several Ψ synthases can act on mRNA
- Pseudouridine synthases in humans
- PUS10 shows high co-expression with microprocessor
- Model for microRNA biogenesis
- Is Ψ activity of PUS10 important for miRNA biogenesis?
- PUS10 binds to pri-miRNA in vivo
- PUS10 binds to pri-miRNA in vitro
- PUS10 also binds to microprocessor
- PUS10 may act as a scaffold protein
- PUS10-KD mESCs exhibit a clear defect in differentiation
- PUS10: differential roles revealed
- Other human pseudouridine synthases
- PUS upregulation indicates poor prognosis in GBM patients
- PUS regulates tumorigenicity in vivo
- PUS-dependent ψ affects translation
- An inhibitor of ψ synthase suppresses tumor growth & promotes survival
- N6,2’-O-dimethyladenosine (m6Am)
- An in vitro m6Am methylation assay
- Identification of a candidate m6Am writer: PCIF1
- Robust activity of recombinant PCIF1 protein in vitro
- In vivo m6Am methylation activity of PCIF1
- In vivo targets of PCIF1 using m6A-seq
- m6Am vs. mRNA expression level
- Mapping m6Am and m6A methylome in human tissues
- The distribution pattern and consensus motif of m6Am & m6A
- m6Am methylome across different human tissues
- m6Am methylome across different mouse tissues
- m6Am methylome conservation across species
- m6Am/m6A signals in “writers” and “erasers”
- Functional and mechanistic hypothesis of m6Am
- m6Am-seq: an m6Am-specific epitranscriptomic method
- m6Am-seq detects m6Am directly and specifically
- m6Am-seq is sensitive and robust
- m6Am-seq detects 5’-UTR m6A
- Ongoing study enabled by m6Am-seq
- A new territory of epitranscriptomics
- Epitranscriptome: dynamic, reversible and conserved
- Acknowledgements
Topics Covered
- RNA modifications in Human Disease
- Pseudouridine
- Molecular Genetics
- Cancer Genetics
- Epitranscriptomics
- Gene Regulation
- Research Methodology
Talk Citation
Yi, C. (2021, June 29). RNA modifications in human diseases: what, when and how? [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/IFLM3878.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Chengqi Yi has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Genetics & Epigenetics
Transcript
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0:00
Hello everyone, I would like to thank
Henry Stewart Talks for inviting me to give this webinar.
My name is Chengqi Yi from Peking University, China.
I will talk about RNA modifications in biology and human diseases,
and share with you some of our recent work in the field of epitranscriptomics.
0:20
According to the central dogma, RNA is not only the carrier of genetic code,
but also controls the flow of genetic information.
To function properly RNA has to be chemically modified.
In fact, over 160 different types of RNA modifications have been identified so far.
Growing evidence has demonstrated that RNA modifications, and the enzymes
catalyzing such modifications, play important roles in various human diseases, including
(but not limited to) cancer, neurological disorders,
immune diseases, and mitochondrial-linked disorders.
Take m^6A for instance, it is the most abundant internal mRNA modification in higher eukaryotes,
and mutation or dysregulation of m^6A writers, erasers, and readers,
have been shown to be the direct cause of multiple diseases.
However, for the most part of RNA modifications,
the molecular mechanisms behind these connections remain unclear.
1:26
My research focuses on RNA modification mediating gene expression regulation.
We ask: what modifications are biologically important and disease-relevant?
In addition to the well-known m^6A, there are about a dozen mRNA modifications in human cells,
including m^6Am, pseudouridine, m^1A etc.
To understand their biology, we first want to know where these modifications are in the transcriptome.
Utilizing our expertise in chemical biology,
we have developed several technologies to review the landscape of these RNA modifications.
Such enabling technologies have, in turn,
facilitated functional and mechanistic study to
understand how these modifications can impact gene expression.
Today, I will share with you our findings on pseudouridine and m^6Am.