Molecular Cell Cover Story: Long Noncoding RNAs with snoRNA Ends Trap Fox to Regulate Splicing
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Time: 2012-10-26
Long noncoding RNAs (lncRNAs) are emerging as a major class of eukaryotic transcripts with diverse roles in modulating gene expression. Now researchers from Chinese Academy of Sciences discovered a novel class of intron-derived and snoRNA-capped lncRNAs (named sno-lncRNAs). The most abundant sno-lncRNAs in pluripotent cells are produced from the Prader-Willi Syndrome (PWS) deletion region (15q11-q13) and play a role in splicing regulation by trapping Fox2. These findings demonstrate a new mechanism of lncRNA processing and implicate such molecules in the molecular pathogenesis of PWS.
To discover new lncRNA species, researchers led by Dr. CHEN Lingling from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in collaboration with scientists from CAS-MPG Partner Institute for Computational Biology and University of Connecticut Health Center, USA, have employed a variety of techniques including deep sequencing to explore the repertoire of non-polyadenylated RNAs isolated from human embryonic stem cells (hESCs). These studies allowed them to uncover a new member of the non-coding RNA family: sno-lncRNAs, which are derived from introns carrying snoRNAs on their ends. During exonucleolytic trimming, the sequences between the snoRNAs are not degraded, leading to the accumulation of lncRNAs flanked by snoRNA sequences but lacking 5’ caps and 3’ poly(A) tails.
Importantly, the genomic region encoding one most abundant class of sno-lncRNAs (15q11-q13) is specifically deleted in Prader-Willi Syndrome, a multiple-system human disorder including global developmental delay, mental retardation, morbid obesity, and etc. In hESCs, PWS region sno-lncRNAs accumulate near their sites of synthesis and associate strongly with the alternative splicing regulator Fox2. These sno-lncRNAs act as “molecular sinks” to sequester Fox2 and alter patterns of alternative splicing, implicating a previously unannotated class of lncRNAs in PWS pathogenesis during early embryonic development and adulthood.
The study entitled "Long noncoding RNAs with snoRNA ends" has been published as a Cover Story in Molecular Cell on October 26th, 2012, featured in Preview Article as an Issue Highlight in the same issue, and also highlighted by Nature Reviews Molecular Cell Biology.
The study was funded by Ministry of Science and Technology of China and Chinese Academy of Sciences.
CONTACT:
CHEN Lingling
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Email: linglingchen@sibcb.ac.cn Tel: +86-21-54921021
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