p53 mediates target gene association with nuclear speckles for amplified RNA expression

Katherine A. Alexander, Allison Coté, Son C. Nguyen, Liguo Zhang, Omid Gholamalamdari, Paula Agudelo-Garcia, Enrique Lin-Shiao, K. M.A. Tanim, Joan Lim, Nicolas Biddle, Margaret C. Dunagin, Charly R. Good, Mariel R. Mendoza, Shawn C. Little, Andrew Belmont, Eric F. Joyce, Arjun Raj, Shelley L. Berger

Research output: Contribution to journalArticlepeer-review

Abstract

Nuclear speckles are prominent nuclear bodies that contain proteins and RNA involved in gene expression. Although links between nuclear speckles and gene activation are emerging, the mechanisms regulating association of genes with speckles are unclear. We find that speckle association of p53 target genes is driven by the p53 transcription factor. Focusing on p21, a key p53 target, we demonstrate that speckle association boosts expression by elevating nascent RNA amounts. p53-regulated speckle association did not depend on p53 transactivation functions but required an intact proline-rich domain and direct DNA binding, providing mechanisms within p53 for regulating gene-speckle association. Beyond p21, a substantial subset of p53 targets have p53-regulated speckle association. Strikingly, speckle-associating p53 targets are more robustly activated and occupy a distinct niche of p53 biology compared with non-speckle-associating p53 targets. Together, our findings illuminate regulated speckle association as a mechanism used by a transcription factor to boost gene expression.

Original languageEnglish (US)
Pages (from-to)1666-1681.e6
JournalMolecular cell
Volume81
Issue number8
DOIs
StatePublished - Apr 15 2021

Keywords

  • chromosome architecture
  • gene activation
  • nuclear positioning
  • nuclear speckles
  • p21
  • p53
  • phase-separated nuclear bodies
  • transcription
  • transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'p53 mediates target gene association with nuclear speckles for amplified RNA expression'. Together they form a unique fingerprint.

Cite this