2012
DOI: 10.1126/science.1228110
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Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing

Abstract: Mammalian imprinted genes often cluster with long noncoding (lnc) RNAs. Three lncRNAs that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous lncRNA to different lengths. The results excluded a role for spliced and unspliced Airn lncRNA products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn … Show more

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Cited by 491 publications
(418 citation statements)
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“…Most of these eukaryotic lncRNAs function in trans to silence gene expression directly. However, for at least one of these lncRNAs, Airn, the gene silencing mechanism is different (41). Like the RpoN-dependent prokaryotic crl lncRNA, the mammalian Airn lncRNA is nonfunctional; it is the act of making these lncRNAs, not the lncRNA themselves, that is responsible for gene silencing.…”
Section: Discussionmentioning
confidence: 99%
“…Most of these eukaryotic lncRNAs function in trans to silence gene expression directly. However, for at least one of these lncRNAs, Airn, the gene silencing mechanism is different (41). Like the RpoN-dependent prokaryotic crl lncRNA, the mammalian Airn lncRNA is nonfunctional; it is the act of making these lncRNAs, not the lncRNA themselves, that is responsible for gene silencing.…”
Section: Discussionmentioning
confidence: 99%
“…This result is reminiscent of Air (Airn), which also functions in mechanistically distinct cis and trans roles to regulate gene expression. 54,55 Dbp2 is a co-transcriptional RNA chaperone and bona fide RNA helicase whose activity is necessary for assembly of RNAbinding proteins, Yra1, Mex67, and Nab2 onto poly(A) C RNAs. 56,57 During transcription, both messenger and long non-coding RNAs are co-transcriptionally bound with a set of RNA-binding proteins to form a ribonucleoprotein complex (RNP), which then undergoes a variety of processing steps, including capping, splicing, termination, and polyadenylation.…”
mentioning
confidence: 99%
“…Airn-mediated silencing occurs by at least two different mechanisms. In the case of Igf2r, transcription alone is sufficient to induce silencing [117]. Conversely, Slc22a3 silencing is dependent upon Airn-dependent recruitment of EHMT2 (a H3K9 histone methylase also known as G9a) [118].…”
Section: Long Non-coding Rnas Are Involved In Neural Development and mentioning
confidence: 99%