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Long non-coding (lnc) RNAs can regulate gene expression and protein functions. However, the proportion of lncRNAs with biological activities among the thousands expressed in mammalian cells is controversial. We studied Lockd (lncRNA downstream of Cdkn1b), a 434-nt polyadenylated lncRNA originating 4 kb 3' to the Cdkn1b gene. Deletion of the 25-kb Lockd locus reduced Cdkn1b transcription by approximately 70% in an erythroid cell line. In contrast, homozygous insertion of a polyadenylation cassette 80 bp downstream of the Lockd transcription start site reduced the entire lncRNA transcript level by >90% with no effect on Cdkn1b transcription. The Lockd promoter contains a DNase-hypersensitive site, binds numerous transcription factors, and physically associates with the Cdkn1b promoter in chromosomal conformation capture studies. Therefore, the Lockd gene positively regulates Cdkn1b transcription through an enhancer-like cis element, whereas the lncRNA itself is dispensable, which may be the case for other lncRNAs.

Original publication

DOI

10.1016/j.molcel.2016.02.029

Type

Journal article

Journal

Mol Cell

Publication Date

07/04/2016

Volume

62

Pages

104 - 110

Keywords

Animals, Cell Line, Cyclin-Dependent Kinase Inhibitor p27, Enhancer Elements, Genetic, Gene Expression Regulation, Mice, Poly A, Promoter Regions, Genetic, RNA, Long Noncoding, Transcription, Genetic