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Title: Intergenic long noncoding RNAs provide a novel layer of post-transcriptional regulation in development and disease
Author: Tan, Jennifer Yihong
ISNI:       0000 0004 5369 3752
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2014
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Recent genome-wide sequencing projects revealed the pervasive transcription of intergenic long noncoding RNAs (lincRNAs) in eukaryotic genomes (reviewed in Ponting et al. 2009). For the vast majority of lincRNAs, their mechanisms of function remain largely unrecognized. However, the genome-wide signatures of functionality associated with many lincRNAs, including apparent evolutionary sequence conservation, spatial and temporal-restricted expression patterns, strong associations with epigenetic marks, and reported molecular and cellular functions, reinforce their biological relevance. My work investigates lincRNAs that post-transcriptionally regulate gene abundance by competing for the binding of common microRNAs (miRNAs) with protein-coding transcripts, termed competitive endogenous RNAs (ceRNAs) acting lincRNAs (lnceRNAs). First, I examine the biological relevance of this post-transcriptional regulation of gene abundance by ceRNAs. Next, I estimate the genome-wide prevalence of lnceRNAs in mouse embryonic stem cells (mESCs) and characterize their properties. Finally, using two specific examples of lnceRNAs, I show the contributions of lnceRNAs to human monogenic and complex trait diseases. Collectively, these results illustrate that lnceRNAs provide a novel layer of post-transcriptional regulation via a miRNA-mediated mechanism that contributes to organismal and cellular biology.
Supervisor: Ponting, Chris ; Marques, Ana Sponsor: Oxford University's Clarendon Fund ; Natural Sciences and Engineering Research Council of Canada ; Medical Research Council ; Keble College Sloane-Robinson Clarendon Scholarship
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Life Sciences ; Bioinformatics (life sciences) ; Biology ; Medical Sciences ; Genetics (medical sciences) ; Neuroscience ; Autism ; microRNA ; noncoding RNA ; long noncoding RNA ; competitive endogenous RNA ; autism spectrum disorders ; Spinocerebellar ataxia type 7 ; mouse embryonic stem cells