Transcriptomics,Genomics

Dataset Information

359

A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure.


ABSTRACT: Prader-Willi syndrome (PWS), a genetic cause of childhood obesity, is characterized by intellectual disabilities and sleep abnormalities. PWS-causing deletions include a neuronal long, non-coding RNA (lncRNA) processed into small nucleolar RNAs and a spliced lncRNA,116HG. We show that 116HG forms a subnuclear RNA cloud that co-purifies with the transcriptional activator RBBP5 and active metabolic genes, remains tethered to the site of its transcription and increases in size in postnatal neurons. Snord116del mice lacking 116HG exhibited increased energy expenditure corresponding to dysregulation of diurnally expressed Mtor and circadian genes Clock, Cry1, and Per2. Genomic and metabolic analyses demonstrate altered diurnal energy regulation in the Snord116del mouse cortex and link the loss of 116HG to the energy imbalance observed in PWS. Examination of lncRNA binding sites by ChIRP-seq using an oligo-based purification method from WT and Snord116del (+/-) mouse brain with specific and nonspecific control oligos. Transcript abundance levels by RNA-seq analysis of 3 adult WT and 2 adult Snord116del (+/-) mouse brain cortices at Zt+6 and 2 adult WT and 2 adult Snord116del (+/-) mouse brain cortices at Zt+16.

ORGANISM(S): Mus musculus  

SUBMITTER: Weston Powell   Weston T Powell 

PROVIDER: E-GEOD-43575 | ArrayExpress | 2013-06-20

SECONDARY ACCESSION(S): GSE43575SRP018013PRJNA186743

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure.

Powell Weston T WT   Coulson Rochelle L RL   Crary Florence K FK   Wong Spencer S SS   Ach Robert A RA   Tsang Peter P   Alice Yamada N N   Yasui Dag H DH   Lasalle Janine M JM  

Human molecular genetics 20130613 21


Prader-Willi syndrome (PWS), a genetic disorder of obesity, intellectual disability and sleep abnormalities, is caused by loss of non-coding RNAs on paternal chromosome 15q11-q13. The imprinted minimal PWS locus encompasses a long non-coding RNA (lncRNA) transcript processed into multiple SNORD116 small nucleolar RNAs and the spliced exons of the host gene, 116HG. However, both the molecular function and the disease relevance of the spliced lncRNA 116HG are unknown. Here, we show that 116HG form  ...[more]

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