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PMID: 24656821 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Systematic identification of regulatory elements in conserved 3' UTRs of human transcripts.

Cell reports ·Vol. 7 ·No. 1 ·2014-04-10 ·Pages 281-92

Oikonomou P, Goodarzi H, Tavazoie S

Abstract

Posttranscriptional regulatory programs governing diverse aspects of RNA biology remain largely uncharacterized. Understanding the functional roles of RNA cis-regulatory elements is essential for decoding complex programs that underlie the dynamic regulation of transcript stability, splicing, localization, and translation. Here, we describe a combined experimental/computational technology to reveal a catalog of functional regulatory elements embedded in 3' UTRs of human transcripts. We used a bidirectional reporter system coupled with flow cytometry and high-throughput sequencing to measure the effect of short, noncoding, vertebrate-conserved RNA sequences on transcript stability and translation. Information-theoretic motif analysis of the resulting sequence-to-gene-expression mapping revealed linear and structural RNA cis-regulatory elements that positively and negatively modulate the posttranscriptional fates of human transcripts. This combined experimental/computational strategy can be used to systematically characterize the vast landscape of posttranscriptional regulatory elements controlling physiological and pathological cellular state transitions.

MeSH Terms
3' Untranslated Regions Animals Computational Biology/methods High-Throughput Nucleotide Sequencing Humans Mice Nucleic Acid Conformation RNA/genetics Regulatory Sequences, Nucleic Acid Transcriptome
Chemicals
3' Untranslated Regions RNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Oikonomou Panos
Joint Centers for Systems Biology, Columbia University, New York, NY 10032, USA.
Goodarzi Hani
Joint Centers for Systems Biology, Columbia University, New York, NY 10032, USA.
Tavazoie Saeed
Joint Centers for Systems Biology, Columbia University, New York, NY 10032, USA; Department of Biochemistry and Molecular Biology, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA. Electronic address: st2744@columbia.edu.
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Article Info
Journal
Cell reports
Abbr.
Cell Rep
ISSN
2211-1247
DOI
10.1016/j.celrep.2014.03.001
Email
st2744@columbia.edu
Published
2014-04-10
Epub
2014-00-20
Pages
281-92
Language
English
Region
United States
NLM ID
101573691
PMCID
PMC4430845
Subset
IM
Grants
NHGRI NIH HHS · R01 HG003219 · United States
NHGRI NIH HHS · 2R01HG003219 · United States
Databases
GEO
GSE55396
External Links
PubMed source DOI: 10.1016/j.celrep.2014.03.001 PMC Full Text View journal details
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