The identification and functional annotation of RNA structures conserved in vertebrates

Ernst Stefan Seemann; Aashiq Hussain Mirza; Claus Hansen; Claus H Bang-Berthelsen; Christian Garde; Mikkel Christensen-Dalsgaard; Elfar Torarinsson; Zizhen Yao; Christopher T Workman; Flemming Pociot; Henrik Nielsen; Niels Tommerup; Walter L. Ruzzo; Jan Gorodkin

doi:10.1101/gr.208652.116

The identification and functional annotation of RNA structures conserved in vertebrates

Ernst Stefan Seemann, Aashiq Hussain Mirza, Claus Hansen, Claus H Bang-Berthelsen, Christian Garde, Mikkel Christensen-Dalsgaard, Elfar Torarinsson, Zizhen Yao, Christopher T Workman, Flemming Pociot, Henrik Nielsen, Niels Tommerup, Walter L. Ruzzo, Jan Gorodkin

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Abstract

Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human-mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.

Original language	English
Journal	Genome Research
Volume	27
Pages (from-to)	1371-1383
Number of pages	14
ISSN	1088-9051
DOIs	https://doi.org/10.1101/gr.208652.116
Publication status	Published - Aug 2017

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The identification and functional annotation of RNA structures conserved in vertebratesFinal published version, 916 KBLicence: CC BY

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Seemann, E. S., Mirza, A. H., Hansen, C., Bang-Berthelsen, C. H., Garde, C., Christensen-Dalsgaard, M., Torarinsson, E., Yao, Z., Workman, C. T., Pociot, F., Nielsen, H., Tommerup, N., Ruzzo, W. L., & Gorodkin, J. (2017). The identification and functional annotation of RNA structures conserved in vertebrates. Genome Research, 27, 1371-1383. https://doi.org/10.1101/gr.208652.116

@article{23df25b3a7b146d7aa13580433815387,

title = "The identification and functional annotation of RNA structures conserved in vertebrates",

abstract = "Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human-mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.",

author = "Seemann, {Ernst Stefan} and Mirza, {Aashiq Hussain} and Claus Hansen and Bang-Berthelsen, {Claus H} and Christian Garde and Mikkel Christensen-Dalsgaard and Elfar Torarinsson and Zizhen Yao and Workman, {Christopher T} and Flemming Pociot and Henrik Nielsen and Niels Tommerup and Ruzzo, {Walter L.} and Jan Gorodkin",

note = "Published by Cold Spring Harbor Laboratory Press.",

year = "2017",

month = aug,

doi = "10.1101/gr.208652.116",

language = "English",

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T1 - The identification and functional annotation of RNA structures conserved in vertebrates

AU - Seemann, Ernst Stefan

AU - Mirza, Aashiq Hussain

AU - Hansen, Claus

AU - Bang-Berthelsen, Claus H

AU - Garde, Christian

AU - Christensen-Dalsgaard, Mikkel

AU - Torarinsson, Elfar

AU - Yao, Zizhen

AU - Workman, Christopher T

AU - Pociot, Flemming

AU - Nielsen, Henrik

AU - Tommerup, Niels

AU - Ruzzo, Walter L.

AU - Gorodkin, Jan

N1 - Published by Cold Spring Harbor Laboratory Press.

PY - 2017/8

Y1 - 2017/8

N2 - Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human-mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.

AB - Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human-mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.

U2 - 10.1101/gr.208652.116

DO - 10.1101/gr.208652.116

M3 - Journal article

C2 - 28487280

SN - 1088-9051

VL - 27

SP - 1371

EP - 1383

JO - Genome Research

JF - Genome Research

ER -

The identification and functional annotation of RNA structures conserved in vertebrates

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