Antisense transcripts are targets for activating small RNAs

Jacob C Schwartz, Scott T. Younger, Ngoc Bich Nguyen, Daniel B. Hardy, Brett P. Monia, David R. Corey, Bethany A. Janowski

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1γ. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.

Original languageEnglish (US)
Pages (from-to)842-848
Number of pages7
JournalNature Structural and Molecular Biology
Volume15
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

Progesterone Receptors
RNA
Gene Expression
Argonaute Proteins
Heterogeneous-Nuclear Ribonucleoproteins
Complementary RNA
RNA Polymerase II
Genetic Promoter Regions
Messenger RNA

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Schwartz, J. C., Younger, S. T., Nguyen, N. B., Hardy, D. B., Monia, B. P., Corey, D. R., & Janowski, B. A. (2008). Antisense transcripts are targets for activating small RNAs. Nature Structural and Molecular Biology, 15(8), 842-848. https://doi.org/10.1038/nsmb.1444

Antisense transcripts are targets for activating small RNAs. / Schwartz, Jacob C; Younger, Scott T.; Nguyen, Ngoc Bich; Hardy, Daniel B.; Monia, Brett P.; Corey, David R.; Janowski, Bethany A.

In: Nature Structural and Molecular Biology, Vol. 15, No. 8, 08.2008, p. 842-848.

Research output: Contribution to journalArticle

Schwartz, JC, Younger, ST, Nguyen, NB, Hardy, DB, Monia, BP, Corey, DR & Janowski, BA 2008, 'Antisense transcripts are targets for activating small RNAs', Nature Structural and Molecular Biology, vol. 15, no. 8, pp. 842-848. https://doi.org/10.1038/nsmb.1444
Schwartz, Jacob C ; Younger, Scott T. ; Nguyen, Ngoc Bich ; Hardy, Daniel B. ; Monia, Brett P. ; Corey, David R. ; Janowski, Bethany A. / Antisense transcripts are targets for activating small RNAs. In: Nature Structural and Molecular Biology. 2008 ; Vol. 15, No. 8. pp. 842-848.
@article{96b3baad0d7446f8be3a9eb346a3e71d,
title = "Antisense transcripts are targets for activating small RNAs",
abstract = "Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1γ. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.",
author = "Schwartz, {Jacob C} and Younger, {Scott T.} and Nguyen, {Ngoc Bich} and Hardy, {Daniel B.} and Monia, {Brett P.} and Corey, {David R.} and Janowski, {Bethany A.}",
year = "2008",
month = "8",
doi = "10.1038/nsmb.1444",
language = "English (US)",
volume = "15",
pages = "842--848",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Antisense transcripts are targets for activating small RNAs

AU - Schwartz, Jacob C

AU - Younger, Scott T.

AU - Nguyen, Ngoc Bich

AU - Hardy, Daniel B.

AU - Monia, Brett P.

AU - Corey, David R.

AU - Janowski, Bethany A.

PY - 2008/8

Y1 - 2008/8

N2 - Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1γ. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.

AB - Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1γ. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.

UR - http://www.scopus.com/inward/record.url?scp=49449117338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49449117338&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1444

DO - 10.1038/nsmb.1444

M3 - Article

VL - 15

SP - 842

EP - 848

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 8

ER -