Cited by 570RNA and protein synthesis mechanismsRNA Research and SplicingRNA regulation and disease

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Landscape and variation of RNA secondary structure across the human transcriptome

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Wan, Yue, Qu, Kun, Zhang, Qiangfeng Cliff, Flynn, Ryan A., Manor, Ohad, Ouyang, Zhengqing, Zhang, Jiajing, Spitale, Robert C., Snyder, Michael P., Segal, Eran, Chang, Howard Y.·2014·Nature

DOI 10.1038/nature12946PMC PMC3973747

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Abstract

In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.

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Authors: Wan, Y., Qu, K., Zhang, Q. C., Flynn, R. A., Manor, O., Ouyang, Z., Zhang, J., Spitale, R. C., Snyder, M. P., Segal, E., & Chang, H. Y.
Affiliations: Howard Hughes Medical Institute (US)
Weizmann Institute of Science (IL)
Stanford Medicine (US)
Corresponding author: Wan, Yue
Chang, Howard Y.
ORCID: Wan, Yue
Qu, Kun
Zhang, Qiangfeng Cliff
Flynn, Ryan A.
Manor, Ohad
Ouyang, Zhengqing
Zhang, Jiajing
Spitale, Robert C.
Snyder, Michael P.
Segal, Eran
Chang, Howard Y.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2014-01-29
Volume: 505
Issue: 7485
Pages: 706-709
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature12946
PMC: PMC3973747
OpenAlex: W2071717527
Cited by: 555
References: 26
Citations by year: 2026: 29 · 2025: 24 · 2024: 26 · 2023: 30 · 2022: 40 · 2021: 50 · 2020: 52 · 2019: 37 · 2018: 61 · 2017: 40 · 2016: 56 · 2015: 71 · 2014: 39
FWCI: 28.31
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders: Howard Hughes Medical Institute
National Human Genome Research Institute (R01HG004361)
National Cancer Institute (T32CA009302, P30CA034196)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: RNA secondary structure, human transcriptome, single nucleotide variants, RNA structure prediction, gene expression regulation, single-stranded RNA, Arabidopsis thaliana, yeast, non-coding RNA, splice sites, polyadenylation
MeSH terms: Base Sequence, Binding Sites, Child, Female, Gene Expression Regulation, Humans, Male, Nucleic Acid Conformation, RNA, Genome, Human, Open Reading Frames, RNA-Binding Proteins, Point Mutation, 3' Untranslated Regions, RNA Splice Sites, MicroRNAs, Transcriptome

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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Landscape and variation of RNA secondary structure across the human transcriptome

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

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