Functional elements of the cis-regulatory lincRNA-p21

Lauren Winkler, Maria Jimenez, Joshua T. Zimmer, Adam Williams, Matthew D. Simon, Nadya Dimitrova*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The p53-induced long noncoding RNA (lncRNA) lincRNA-p21 is proposed to act in cis to promote p53-dependent expression of the neighboring cell cycle gene, Cdkn1a/p21. The molecular mechanism through which the transcribed lincRNA-p21 regulatory locus activates p21 expression remains poorly understood. To elucidate the functional elements of cis-regulation, we generate a series of genetic models that disrupt DNA regulatory elements, the transcription of lincRNA-p21, or the accumulation of mature lincRNA-p21. Unexpectedly, we determine that full-length transcription, splicing, and accumulation of lincRNA-p21 are dispensable for the chromatin organization of the locus and for cis-regulation. Instead, we find that production of lincRNA-p21 through conserved regions in exon 1 of lincRNA-p21 promotes cis-activation. These findings demonstrate that the activation of nascent transcription from this lncRNA locus, but not the generation or accumulation of a mature lncRNA transcript, is necessary to enact local gene expression control.

Original languageEnglish (US)
Article number110687
JournalCell reports
Volume39
Issue number3
DOIs
StatePublished - Apr 19 2022

Keywords

  • CP: Molecular biology
  • cis-regulation
  • genetic models
  • lincRNA-p21
  • long noncoding RNA
  • transcription

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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