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Poly(rC)-binding protein 1 (PCBP1)–Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA regulatory complex (PCBP1–CFTR mRNA complex)

Target
PCBP1–CFTR mRNA complex
Molecular classification
Ribonucleoprotein complex, RNA-binding protein complex
01

Overview

The Poly(rC)-binding protein 1 (PCBP1)–Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA regulatory complex is a ribonucleoprotein assembly involving the PCBP1 protein, also known as hnRNP E1, and the messenger RNA of the CFTR gene [Holla et al., 2015]. PCBP1 binds to specific cytosine-rich (C-rich) elements within the 3' untranslated region (3' UTR) of the CFTR mRNA, where it acts as a critical post-transcriptional regulator [Holla et al., 2015; UniProt: Q15365]. This interaction is essential for determining the stability and translational efficiency of the CFTR transcript, directly influencing the amount of functional CFTR protein produced and localized to the cell membrane [Holla et al., 2015]. In the context of Cystic Fibrosis, where mutations often lead to insufficient protein levels, modulating this complex represents a therapeutic strategy to increase the pool of available CFTR mRNA and protein [Amaral & Farinha, 2013]. Experimental approaches, such as the use of antisense oligonucleotides (ASOs), aim to stabilize the mRNA or enhance translation by targeting the regulatory sites within this complex [Ramalho et al., 2022].

Other names
hnRNP E1–CFTR mRNA complexPCBP1–CFTR 3' UTR complexPoly(rC)-binding protein 1–CFTR transcript interactionhnRNP E1–CFTR interaction
02

Mechanism of action

Stabilization of CFTR mRNA and enhancement of translation through binding to the 3' untranslated region (UTR)

03

Biological functions

mRNA stabilizationTranslational regulationPost-transcriptional gene regulation
04

Disease associations

Cystic Fibrosis
05

Safety considerations

Off-target RNA bindingSystemic disruption of PCBP1-mediated regulation of other transcriptsImmunogenicity of antisense oligonucleotides
06

Interacting drugs

Antisense oligonucleotides (experimental)
07

Biomarkers

CFTR mRNA levelsCFTR protein expressionSweat chloride concentrationNasal potential difference

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