Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality

Evgenia Ntini; Aino I Järvelin; Jette Bornholdt; Yun Chen; Mette Boyd; Mette Jørgensen; Robin Andersson; Ilka Hoof; Aleks Schein; Peter R Andersen; Pia K Andersen; Pascal Preker; Eivind Valen; Xiaobei Zhao; Vicent Pelechano; Lars M Steinmetz; Albin Gustav Sandelin; Torben Heick Jensen

doi:10.1038/nsmb.2640

Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality

Evgenia Ntini, Aino I Järvelin, Jette Bornholdt, Yun Chen, Mette Boyd, Mette Jørgensen, Robin Andersson, Ilka Hoof, Aleks Schein, Peter R Andersen, Pia K Andersen, Pascal Preker, Eivind Valen, Xiaobei Zhao, Vicent Pelechano, Lars M Steinmetz, Albin Gustav Sandelin, Torben Heick Jensen

Institut for Molekylærbiologi og Genetik

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

217 Citationer (Scopus)

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Abstract

Active human promoters produce promoter-upstream transcripts (PROMPTs). Why these RNAs are coupled to decay, whereas their neighboring promoter-downstream mRNAs are not, is unknown. Here high-throughput sequencing demonstrates that PROMPTs generally initiate in the antisense direction closely upstream of the transcription start sites (TSSs) of their associated genes. PROMPT TSSs share features with mRNA-producing TSSs, including stalled RNA polymerase II (RNAPII) and the production of small TSS-associated RNAs. Notably, motif analyses around PROMPT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROMPT pA signals are functional but linked to RNA degradation. Moreover, pA signals are under-represented in promoter-downstream versus promoter-upstream regions, thus allowing for more efficient RNAPII progress in the sense direction from gene promoters. We conclude that asymmetric sequence distribution around human gene promoters serves to provide a directional RNA output from an otherwise bidirectional transcription process.

Originalsprog	Engelsk
Tidsskrift	Nature Structural and Molecular Biology
Vol/bind	20
Nummer	8
Sider (fra-til)	923-928
Antal sider	6
ISSN	1545-9993
DOI	https://doi.org/10.1038/nsmb.2640
Status	Udgivet - 14 jul. 2013

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10.1038/nsmb.2640

Ntini et al. 2013

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Ntini, E., Järvelin, A. I., Bornholdt, J., Chen, Y., Boyd, M., Jørgensen, M., Andersson, R., Hoof, I., Schein, A., Andersen, P. R., Andersen, P. K., Preker, P., Valen, E., Zhao, X., Pelechano, V., Steinmetz, L. M., Sandelin, A. G., & Jensen, T. H. (2013). Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality. Nature Structural and Molecular Biology, 20(8), 923-928. https://doi.org/10.1038/nsmb.2640

@article{35c6a190d6894ee2acf474b100495acc,

title = "Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality",

abstract = "Active human promoters produce promoter-upstream transcripts (PROMPTs). Why these RNAs are coupled to decay, whereas their neighboring promoter-downstream mRNAs are not, is unknown. Here high-throughput sequencing demonstrates that PROMPTs generally initiate in the antisense direction closely upstream of the transcription start sites (TSSs) of their associated genes. PROMPT TSSs share features with mRNA-producing TSSs, including stalled RNA polymerase II (RNAPII) and the production of small TSS-associated RNAs. Notably, motif analyses around PROMPT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROMPT pA signals are functional but linked to RNA degradation. Moreover, pA signals are under-represented in promoter-downstream versus promoter-upstream regions, thus allowing for more efficient RNAPII progress in the sense direction from gene promoters. We conclude that asymmetric sequence distribution around human gene promoters serves to provide a directional RNA output from an otherwise bidirectional transcription process.",

keywords = "Base Sequence, Blotting, Northern, HeLa Cells, High-Throughput Nucleotide Sequencing, Humans, Molecular Sequence Data, Oligonucleotides, Polyadenylation, Promoter Regions, Genetic, RNA Polymerase II, RNA Stability, Transcription Initiation Site, Transcription, Genetic",

author = "Evgenia Ntini and J{\"a}rvelin, {Aino I} and Jette Bornholdt and Yun Chen and Mette Boyd and Mette J{\o}rgensen and Robin Andersson and Ilka Hoof and Aleks Schein and Andersen, {Peter R} and Andersen, {Pia K} and Pascal Preker and Eivind Valen and Xiaobei Zhao and Vicent Pelechano and Steinmetz, {Lars M} and Sandelin, {Albin Gustav} and Jensen, {Torben Heick}",

year = "2013",

month = jul,

day = "14",

doi = "10.1038/nsmb.2640",

language = "English",

volume = "20",

pages = "923--928",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Research",

number = "8",

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Ntini, E, Järvelin, AI, Bornholdt, J, Chen, Y, Boyd, M, Jørgensen, M, Andersson, R, Hoof, I, Schein, A, Andersen, PR , Andersen, PK, Preker, P, Valen, E, Zhao, X, Pelechano, V, Steinmetz, LM, Sandelin, AG & Jensen, TH 2013, 'Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality', Nature Structural and Molecular Biology, bind 20, nr. 8, s. 923-928. https://doi.org/10.1038/nsmb.2640

Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality. / Ntini, Evgenia; Järvelin, Aino I; Bornholdt, Jette et al.
I: Nature Structural and Molecular Biology, Bind 20, Nr. 8, 14.07.2013, s. 923-928.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality

AU - Ntini, Evgenia

AU - Järvelin, Aino I

AU - Bornholdt, Jette

AU - Chen, Yun

AU - Boyd, Mette

AU - Jørgensen, Mette

AU - Andersson, Robin

AU - Hoof, Ilka

AU - Schein, Aleks

AU - Andersen, Peter R

AU - Andersen, Pia K

AU - Preker, Pascal

AU - Valen, Eivind

AU - Zhao, Xiaobei

AU - Pelechano, Vicent

AU - Steinmetz, Lars M

AU - Sandelin, Albin Gustav

AU - Jensen, Torben Heick

PY - 2013/7/14

Y1 - 2013/7/14

N2 - Active human promoters produce promoter-upstream transcripts (PROMPTs). Why these RNAs are coupled to decay, whereas their neighboring promoter-downstream mRNAs are not, is unknown. Here high-throughput sequencing demonstrates that PROMPTs generally initiate in the antisense direction closely upstream of the transcription start sites (TSSs) of their associated genes. PROMPT TSSs share features with mRNA-producing TSSs, including stalled RNA polymerase II (RNAPII) and the production of small TSS-associated RNAs. Notably, motif analyses around PROMPT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROMPT pA signals are functional but linked to RNA degradation. Moreover, pA signals are under-represented in promoter-downstream versus promoter-upstream regions, thus allowing for more efficient RNAPII progress in the sense direction from gene promoters. We conclude that asymmetric sequence distribution around human gene promoters serves to provide a directional RNA output from an otherwise bidirectional transcription process.

AB - Active human promoters produce promoter-upstream transcripts (PROMPTs). Why these RNAs are coupled to decay, whereas their neighboring promoter-downstream mRNAs are not, is unknown. Here high-throughput sequencing demonstrates that PROMPTs generally initiate in the antisense direction closely upstream of the transcription start sites (TSSs) of their associated genes. PROMPT TSSs share features with mRNA-producing TSSs, including stalled RNA polymerase II (RNAPII) and the production of small TSS-associated RNAs. Notably, motif analyses around PROMPT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROMPT pA signals are functional but linked to RNA degradation. Moreover, pA signals are under-represented in promoter-downstream versus promoter-upstream regions, thus allowing for more efficient RNAPII progress in the sense direction from gene promoters. We conclude that asymmetric sequence distribution around human gene promoters serves to provide a directional RNA output from an otherwise bidirectional transcription process.

KW - Base Sequence

KW - Blotting, Northern

KW - HeLa Cells

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Molecular Sequence Data

KW - Oligonucleotides

KW - Polyadenylation

KW - Promoter Regions, Genetic

KW - RNA Polymerase II

KW - RNA Stability

KW - Transcription Initiation Site

KW - Transcription, Genetic

U2 - 10.1038/nsmb.2640

DO - 10.1038/nsmb.2640

M3 - Journal article

C2 - 23851456

SN - 1545-9993

VL - 20

SP - 923

EP - 928

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 8

ER -

Polyadenylation site-induced decay of upstream transcripts enforces promoter directionality

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