Gideon Rechavi
Affiliations
Sheba Cancer Research Center, Tel Hashomer
Sackler School of Medicine, Tel Aviv University
Biography
Gideon Rechavi's interest in the last decade focuses on RNA editing and modifications. His research pioneered the identification of global Adenosine to Inosine RNA editing and the deciphering of the m6A methylome. His group is studying the basic mechanisms involved in "epitranscriptomics", the role of RNA editing and modifications in normal development and their derangement in cancer and neurodegenerative disorders. He received his MD from Tel‑Aviv University and PhD from the Weizmann Institute of Science. He is board certified in Pediatrics, Hematology and Pediatric Oncology and holds the Djerassi Chair in Oncology, Tel Aviv University. He established and headed the Pediatric Hematology‑ Oncology and BMT Department as well as the Wiesel Pediatric Hospice at the Sheba Medical Center. He established the Sheba Cancer Research Center which he heads.
He has been awarded numerous prizes including the Kennedy, the Stein and the Seroussi Cancer Research awards, the prize for Vision in Medicine, the Elkales Prize for Distinctive Scientist in Medicine, the EMET prize for Genetics and the Beutler award for Excellence in Genomic Medicine.
Abstract
Epitranscriptomics enters the clinic
Gidi Rechavi
The vocabulary of RNA is extended far beyond the four A,C,G,U letters with more than one hundred modified nucleotides which allow the various RNA molecules to mediate their highly versatile functions. The coming of age of powerful technologies, in particular next generation sequencing, now enables the global mapping of the various modifications and the study of their biological role.
Adenosine to Inosine (A-to-I) RNA editing was known for about fifteen years to affect the coding region of a handful of genes. Combining bioinformatics and experimental validation we demonstrated that this type of RNA modification affects tens of thousands of sites in the human transcriptome involving hundreds of genes. RNA editing has been linked to recoding, alternative splicing, nuclear retention, and microRNA biogenesis and expression control.
N6-methyladenosine (m6A) is the most common internal mRNA modification found in eukaryotic organisms. Using a novel approach, m6A-seq, based on antibody-mediated capture and massively parallel sequencing we characterized the human and mouse methylomes and identified over 12,000 m6A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks, around stop codons and within long internal exons. m6A decoration was found to be involved in regulation of alternative splicing, RNA stability, localization and translation efficiency.
Recent findings shed light on the role of these RNA modifications in early development and on the effect of their perturbation in disease states such as cancer, obesity and neurodegeneration.
