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

Alexander, Katherine A, Coté, Allison, Nguyen, Son C, Zhang, Liguo, Gholamalamdari, Omid, Agudelo-Garcia, Paula, Lin-Shiao, Enrique, Tanim, KMA, Lim, Joan, Biddle, Nicolas, Dunagin, Margaret C, Good, Charly R, Mendoza, Mariel R, Little, Shawn C, Belmont, Andrew, Joyce, Eric F, Raj, Arjun, Berger, Shelley L (April 2021) p53 mediates target gene association with nuclear speckles for amplified RNA expression. Molecular Cell, 81 (8). 1666-1681.e6. ISSN 1097-2765

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function organs, tissues, organelles, cell types and functions > organelles, types and functions > nucleus organs, tissues, organelles, cell types and functions > organelles, types and functions organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Alexander, Katherine
Communities:	CSHL labs > Alexander lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 April 2021
Date Deposited:	16 Jul 2024 13:53
Last Modified:	16 Jul 2024 13:53
PMCID:	PMC8830378
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41607

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