Functional elements of the cis-regulatory lincRNA-p21

Lauren Winkler; Maria Jimenez; Joshua T Zimmer; Adam Williams; Matthew D Simon; Nadya Dimitrova

doi:10.1016/j.celrep.2022.110687

Functional elements of the cis-regulatory lincRNA-p21

Cell Rep. 2022 Apr 19;39(3):110687. doi: 10.1016/j.celrep.2022.110687.

Authors

Lauren Winkler¹, Maria Jimenez¹, Joshua T Zimmer², Adam Williams³, Matthew D Simon², Nadya Dimitrova⁴

Affiliations

¹ Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
² Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA; Institute for Biomolecular Design and Discovery, Yale University, West Haven, CT 06516, USA.
³ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
⁴ Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA. Electronic address: nadya.dimitrova@yale.edu.

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.

Keywords: CP: Molecular biology; cis-regulation; genetic models; lincRNA-p21; long noncoding RNA; transcription.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

RNA, Long Noncoding
Tumor Suppressor Protein p53

Abstract

Publication types

MeSH terms

Substances

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