PABPC1

PABPC1

Overview

Polyadenylate-binding protein 1 (PABPC1) is a protein encoded by the PABPC1 gene in humans. It is a member of the poly(A)-binding protein family, which plays a crucial role in the regulation of mRNA stability and translation. PABPC1 is ubiquitously expressed in eukaryotic cells and is primarily located in the cytoplasm.

Function

PABPC1 binds to the poly(A) tail of mRNA molecules, which is a stretch of adenine nucleotides added to the 3' end of mRNA transcripts. This binding is essential for various aspects of mRNA metabolism, including stabilization, translation initiation, and regulation of mRNA decay. PABPC1 interacts with other proteins involved in translation, such as eukaryotic initiation factors and ribosomal proteins, to facilitate the recruitment of ribosomes to mRNA.

Structure

PABPC1 contains multiple RNA recognition motifs (RRMs) that enable it to bind to the poly(A) tail of mRNA. The protein typically has four RRMs, which are responsible for its high affinity and specificity for polyadenylated RNA. Additionally, PABPC1 has a C-terminal domain that interacts with other proteins involved in mRNA processing and translation.

Role in Translation

PABPC1 plays a pivotal role in the initiation of translation by interacting with the eukaryotic initiation factor 4G (eIF4G), a component of the eIF4F complex. This interaction helps circularize the mRNA, bringing the 5' cap and 3' poly(A) tail into proximity, which enhances the efficiency of translation initiation. PABPC1 also competes with other proteins, such as cytoplasmic polyadenylation element-binding protein (CPEB), to regulate the translation of specific mRNAs.

Regulation of mRNA Stability

PABPC1 is involved in the regulation of mRNA stability by protecting mRNA from rapid degradation. It competes with deadenylase complexes that shorten the poly(A) tail, thereby preventing mRNA decay. The interaction of PABPC1 with other proteins, such as AU-rich element-binding proteins, can influence the stability and turnover of specific mRNAs.

Clinical Significance

Alterations in PABPC1 expression or function have been implicated in various diseases. Overexpression of PABPC1 has been observed in certain types of cancer, where it may contribute to the dysregulation of mRNA translation and stability, promoting tumor growth and progression. Conversely, reduced PABPC1 activity can lead to defects in mRNA processing and translation, potentially resulting in developmental disorders or neurodegenerative diseases.

Research and Future Directions

Ongoing research is focused on understanding the precise mechanisms by which PABPC1 regulates mRNA metabolism and its role in disease. Studies are exploring the potential of targeting PABPC1 or its interacting partners as therapeutic strategies for cancer and other diseases associated with aberrant mRNA regulation.

See Also

• Poly(A)-binding protein
• mRNA stability
• Translation (biology)
• Gene expression regulation

References

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External Links

• [GeneCards: PABPC1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PABPC1)
• [UniProt: PABPC1](https://www.uniprot.org/uniprot/P11940)