The Dimensions, Dynamics, and Relevance of the Mammalian Noncoding Transcriptome. Issue 7 (July 2017)

• Record Type: Journal Article
• Authors: Deveson, Ira W.; Hardwick, Simon A.; Mercer, Tim R.; Mattick, John S.
• Is Part Of: Trends in genetics. Volume 33:Issue 7(2017)
• Page Start: 464
• Page End: 478
• Publication Date: 2017-07
• Subjects: pervasive transcription -- long noncoding RNAs (lncRNAs) -- alternative splicing -- RNA regulation; Genetics -- Periodicals; 576.5
• DOI: 10.1016/j.tig.2017.04.004
• Languages: English
• ISSNs: 0168-9525

Abstract

Abstract : The combination of pervasive transcription and prolific alternative splicing produces a mammalian transcriptome of great breadth and diversity. The majority of transcribed genomic bases are intronic, antisense, or intergenic to protein-coding genes, yielding a plethora of short and long non-protein-coding regulatory RNAs. Long noncoding RNAs (lncRNAs) share most aspects of their biogenesis, processing, and regulation with mRNAs. However, lncRNAs are typically expressed in more restricted patterns, frequently from enhancers, and exhibit almost universal alternative splicing. These features are consistent with their role as modular epigenetic regulators. We describe here the key studies and technological advances that have shaped our understanding of the dimensions, dynamics, and biological relevance of the mammalian noncoding transcriptome. Trends: The mammalian transcriptome is hugely diverse owing to pervasive transcription and alternative splicing. Advances in RNA-Seq (e.g., targeted, single-molecule, and single-cell techniques) continue to shape our understanding. lncRNA diversity remains under-appreciated, and the dynamics of lncRNA expression, splicing, and functional roles remain poorly characterized. High-resolution and single-cell studies show that lncRNAs are not poorly expressed but are expressed with heightened spatiotemporal precision. lncRNAs are also enriched for splicing, with near-universal alternative splicing of noncoding exons. The emergence of high-throughput forward-genetic screens utilizing CRISPR/Cas9 targeted genome manipulation and precise, scalable methods for resolving RNA structure and RNA–protein interactions has accelerated lncRNA characterization. Precise, dynamic expression and complex splicing fit with central role of lncRNAs in the mammalian developmental program.