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Title:
uc.106 is a bona fide tumor suppressor for B-lymphomagenesis |
Abstract:
The initiation and progression of B-cell lymphomas are intricately regulated by various factors. Long noncoding RNAs (lncRNAs) might be one of them. Transcribed ultraconserved regions (T-UCRs) are a novel class of long noncoding RNAs that are highly conserved among the orthologous regions in most vertebrates. Here, we investigated the potential role of ultraconserved RNA uc.106 originating from an intron area in the OLA1 gene. We use a gene knockout strategy to demonstrate that targeted depletion of the uc.106 initiates B-lymphomagenesis in aged mice. Mechanistically, we find that uc106 interacts with Methyltransferase like 3 (METTL3). Deletion of uc.106 leads to enhanced nuclear translocation of METTL3 and elevated m6A modification of mRNAs, resulting in increased Myc stability and expression. Further analysis indicates that uc.106 expression is negatively correlated with m6A and Myc expression in B-lymphoma tissues. Our findings confirm, for the first time, that uc.106 is a bona fide tumor suppressor and plays an important role in B-lymphomagenesis. Targeting the uc.106/METTL3/Myc pathway might have great potential to treat B-lymphomas.
Keywords: B-lymphoma, ultraconserved RNA, uc.106, METTL3, m6A, Myc
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Biography:
Duonan Yu, Ph.D.
Dr. Yu is a specially appointed professor of Jiangsu Province and the Director of Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research. Dr. Yu obtained his Ph.D. in Developmental Biology from the University of Wisconsin-Madison and finished his post-doctoral training at the University of Pennsylvania. He was a Senior Research Investigator at the University of Pennsylvania before returning to China in 2012. His research focuses on the role of non-coding RNA in hematopoietic diseases and normal hematopoietic development. He has published more than 70 peer-reviewed papers including research articles in 《Nature Genetics》,《Genes & Development》,《Blood》,《Cancer Research》,《Haematologica》,《Oncogene》, and《Blood Advances》.
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