A Prader–Willi locus lncRNA cloud modulates diurnal genes and energy expenditure
Open accessAbstract
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 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 post-natal neurons and during sleep. Snord116del mice lacking 116HG exhibited increased energy expenditure corresponding to the dysregulation of diurnally expressed Mtor and circadian genes Clock, Cry1 and Per2. These combined genomic and metabolic analyses demonstrate that 116HG regulates the diurnal energy expenditure of the brain. These novel molecular insights into the energy imbalance in PWS should lead to improved therapies and understanding of lncRNA roles in complex neurodevelopmental and metabolic disorders.
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In mice, paternal deletion of Snord116 increases the expression of several genes specifically during the light phase, including Ube3a, which encodes ubiquitin ligase E3A (UBE3A).
“In mice, paternal deletion of Snord116 increases the expression of several genes specifically during the light phase, including Ube3a, which encodes ubiquitin ligase E3A (UBE3A)116.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [116]
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Rhythms of life: circadian disruption and brain disorders across the lifespan
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- Authors
- Powell, W. T., Coulson, R. L., Crary, F. K., Wong, S. S., Ach, R. A., Tsang, P., Alice Yamada, N., Yasui, D. H., & LaSalle, J. M.
- Affiliations
- University of California, Davis (US)
- Agilent Technologies (United States) (US)
- Corresponding author
- LaSalle, Janine M.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-06-13
- Volume
- 22
- Issue
- 21
- Pages
- 4318-4328
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3792690
- OpenAlex
- W2170561196
- Cited by
- 173
- References
- 46
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 26 · 2023: 4 · 2022: 15 · 2021: 12 · 2020: 10 · 2019: 18 · 2018: 18 · 2017: 9 · 2016: 9 · 2015: 16 · 2014: 19 · 2013: 5
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Human Molecular Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- University of California, Davis
- National Cancer Institute (P30CA093373)
- National Institute of General Medical Sciences (T32GM007377)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK092993)
- National Institute of Neurological Disorders and Stroke (R01NS076263, F31NS073164)
- Genome Center, University of California, Davis
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- Prader-Willi syndrome, long non-coding RNA, RBBP5, energy expenditure, brain energy metabolism, circadian genes, diurnal gene expression, mTOR, clocks, CRY1, Per2, sleep, obesity, neurodevelopmental disorders
- MeSH terms
- Animals, Autopsy, Brain, Circadian Rhythm, DNA-Binding Proteins, Energy Metabolism, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Nuclear Proteins, Prader-Willi Syndrome, Sleep, Genomic Imprinting, Gene Expression Regulation, Developmental, Mice, CLOCK Proteins, Cryptochromes, Period Circadian Proteins, RNA, Long Noncoding
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