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Synthetic biomolecular condensates enhance translation from a target mRNA in living cells.

Publication ,  Journal Article
Shapiro, DM; Deshpande, S; Eghtesadi, SA; Zhong, M; Fontes, CM; Fiflis, D; Rohm, D; Min, J; Kaur, T; Peng, J; Ney, M; Su, J; Dai, Y ...
Published in: Nat Chem
March 2025

Biomolecular condensates composed of proteins and RNA are one approach by which cells regulate post-transcriptional gene expression. Their formation typically involves the phase separation of intrinsically disordered proteins with a target mRNA, sequestering the mRNA into a liquid condensate. This sequestration regulates gene expression by modulating translation or facilitating RNA processing. Here we engineer synthetic condensates using a fusion of an RNA-binding protein, the human Pumilio2 homology domain (Pum2), and a synthetic intrinsically disordered protein, an elastin-like polypeptide (ELP), that can bind and sequester a target mRNA transcript. In protocells, sequestration of a target mRNA largely limits its translation. Conversely, in Escherichia coli, sequestration of the same target mRNA increases its translation. We characterize the Pum2-ELP condensate system using microscopy, biophysical and biochemical assays, and RNA sequencing. This approach enables the modulation of cell function via the formation of synthetic biomolecular condensates that regulate the expression of a target protein.

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Published In

Nat Chem

DOI

EISSN

1755-4349

Publication Date

March 2025

Volume

17

Issue

3

Start / End Page

448 / 456

Location

England

Related Subject Headings

  • RNA-Binding Proteins
  • RNA, Messenger
  • Protein Biosynthesis
  • Peptides
  • Organic Chemistry
  • Intrinsically Disordered Proteins
  • Humans
  • Escherichia coli
  • Elastin
  • Biomolecular Condensates
 

Citation

APA
Chicago
ICMJE
MLA
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Shapiro, D. M., Deshpande, S., Eghtesadi, S. A., Zhong, M., Fontes, C. M., Fiflis, D., … Chilkoti, A. (2025). Synthetic biomolecular condensates enhance translation from a target mRNA in living cells. Nat Chem, 17(3), 448–456. https://doi.org/10.1038/s41557-024-01706-7
Shapiro, Daniel Mark, Sonal Deshpande, Seyed Ali Eghtesadi, Miranda Zhong, Cassio Mendes Fontes, David Fiflis, Dahlia Rohm, et al. “Synthetic biomolecular condensates enhance translation from a target mRNA in living cells.Nat Chem 17, no. 3 (March 2025): 448–56. https://doi.org/10.1038/s41557-024-01706-7.
Shapiro DM, Deshpande S, Eghtesadi SA, Zhong M, Fontes CM, Fiflis D, et al. Synthetic biomolecular condensates enhance translation from a target mRNA in living cells. Nat Chem. 2025 Mar;17(3):448–56.
Shapiro, Daniel Mark, et al. “Synthetic biomolecular condensates enhance translation from a target mRNA in living cells.Nat Chem, vol. 17, no. 3, Mar. 2025, pp. 448–56. Pubmed, doi:10.1038/s41557-024-01706-7.
Shapiro DM, Deshpande S, Eghtesadi SA, Zhong M, Fontes CM, Fiflis D, Rohm D, Min J, Kaur T, Peng J, Ney M, Su J, Dai Y, Asokan A, Gersbach CA, Chilkoti A. Synthetic biomolecular condensates enhance translation from a target mRNA in living cells. Nat Chem. 2025 Mar;17(3):448–456.

Published In

Nat Chem

DOI

EISSN

1755-4349

Publication Date

March 2025

Volume

17

Issue

3

Start / End Page

448 / 456

Location

England

Related Subject Headings

  • RNA-Binding Proteins
  • RNA, Messenger
  • Protein Biosynthesis
  • Peptides
  • Organic Chemistry
  • Intrinsically Disordered Proteins
  • Humans
  • Escherichia coli
  • Elastin
  • Biomolecular Condensates