Genome-wide probing of RNA structures

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Abstract/Contents

Abstract
RNA plays an important role in regulating cellular gene expression. Its ability to fold into secondary and tertiary structures underlies the RNA's ability to function and be processed in every step of its life cycle, including transcription, splicing, cellular localization, translation and turnover of the RNA. However, structural information for most RNAs in the cells, such as mRNAs, is missing due to the low throughput nature of RNA structure probing and the traditional difficulty of probing long RNAs, making it difficult to assess the full impact of RNA structure in biology. To fulfill the need to understand the roles of RNA structure on a global scale, we developed for the first time a novel strategy termed Parallel Analysis of RNA Structure (PARS), which couples structure-specific probing to high throughput sequencing to simultaneously generate secondary structures for thousands of RNA species at single nucleotide resolution. Applying PARS to the yeast transcriptome identified distinct structural organization of mRNAs, including a three nucleotide periodicity in the coding region and increased accessibility near the start codon for translation. Furthermore, we demonstrated that PARS can be used to study dynamics by probing the yeast transcriptome across a temperature gradient to identify functional structural regions that have differential propensity to melt. PARS can be readily applied to different organisms and conditions, to identify structural determinants that regulate gene expression changes across organisms in different cellular states. This expansion of RNA structural data will likely enhance our understanding of how RNA structure translates into RNA function in cellular systems, as well as open doors to potentially targeting these structural elements to regulate cellular behavior in diseases.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Copyright date 2013
Publication date 2012, c2013; 2012
Issuance monographic
Language English

Creators/Contributors

Associated with Wan, Yue
Associated with Stanford University, Cancer Biology Program.
Primary advisor Chang, Howard
Thesis advisor Chang, Howard
Thesis advisor Fire, Andrew Zachary
Thesis advisor Sarnow, P. (Peter)
Thesis advisor Sherlock, Gavin
Advisor Fire, Andrew Zachary
Advisor Sarnow, P. (Peter)
Advisor Sherlock, Gavin

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Yue Wan.
Note Submitted to the Program in Cancer Biology.
Thesis Thesis (Ph.D.)--Stanford University, 2013.
Location electronic resource

Access conditions

Copyright
© 2013 by Yue Wan

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