SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer

Askarian-Amiri, Marjan E., Crawford, Joanna, French, Juliet D., Smart, Chanel E., Smith, Martin A., Clark, Michael B., Ru, Kelin, Mercer, Tim R., Thompson, Ella R., Lakhani, Sunil R., Vargas, Ana C., Campbell, Ian G., Brown, Melissa A., Dinger, Marcel E. and Mattick, John S. (2011) SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA, 17 5: 878-891. doi:10.1261/rna.2528811

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Author Askarian-Amiri, Marjan E.
Crawford, Joanna
French, Juliet D.
Smart, Chanel E.
Smith, Martin A.
Clark, Michael B.
Ru, Kelin
Mercer, Tim R.
Thompson, Ella R.
Lakhani, Sunil R.
Vargas, Ana C.
Campbell, Ian G.
Brown, Melissa A.
Dinger, Marcel E.
Mattick, John S.
Title SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer
Formatted title
SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
1469-9001
Publication date 2011-05
Sub-type Article (original research)
DOI 10.1261/rna.2528811
Open Access Status File (Publisher version)
Volume 17
Issue 5
Start page 878
End page 891
Total pages 14
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2012
Language eng
Formatted abstract
Long noncoding RNAs (lncRNAs) are increasingly recognized to play major regulatory roles in development and disease. To
identify novel regulators in breast biology, we identified differentially regulated lncRNAs during mouse mammary
development. Among the highest and most differentially expressed was a transcript (Zfas1) antisense to the 59 end of the
protein-coding gene Znfx1. In vivo, Zfas1 RNA is localized within the ducts and alveoli of the mammary gland. Zfas1
intronically hosts three previously undescribed C/D box snoRNAs (SNORDs): Snord12, Snord12b, and Snord12c. In contrast
to the general assumption that noncoding SNORD-host transcripts function only as vehicles to generate snoRNAs, knockdown
of Zfas1 in a mammary epithelial cell line resulted in increased cellular proliferation and differentiation, while not
substantially altering the levels of the SNORDs. In support of an independent function, we also found that Zfas1 is extremely
stable, with a half-life >16 h. Expression analysis of the SNORDs revealed these were expressed at different levels, likely
a result of distinct structures conferring differential stability. While there is relatively low primary sequence conservation
between Zfas1 and its syntenic human ortholog ZFAS1, their predicted secondary structures have similar features. Like Zfas1,
ZFAS1 is highly expressed in the mammary gland and is down-regulated in breast tumors compared to normal tissue. We
propose a functional role for Zfas1/ ZFAS1 in the regulation of alveolar development and epithelial cell differentiation in the
mammary gland, which, together with its dysregulation in human breast cancer, suggests ZFAS1 as a putative tumor suppressor
gene.
Keyword Noncoding RNA
snoRNA
Tumor suppressor
Long Noncoding Rnas
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2012 Collection
School of Chemistry and Molecular Biosciences
 
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