CSTF - cleavage stimulation factor subunit | Elisa - Clia - Antibody - Protein

Background

Cleavage stimulation factor (CSTF) is a multi-protein complex essential for the 3'-end processing of pre-mRNA, a critical step in gene expression. CSTF is involved in the cleavage and polyadenylation of pre-mRNA, processes necessary for mRNA maturation and stability. This complex functions at the interface of transcription and mRNA processing, ensuring that newly synthesized mRNAs are properly processed before being exported to the cytoplasm for translation. The CSTF complex is composed of several subunits, each contributing to its function and specificity in recognizing and processing pre-mRNA substrates.

Protein Structure

CSTF is a heterotrimeric complex consisting of three main subunits:

• CSTF-50 (CSTF2): This subunit contains a RNA-binding domain (RBD) and is crucial for recognizing the GU-rich downstream elements of the cleavage site.
• CSTF-64 (CSTF2T): It has an RRM (RNA recognition motif) and plays a role in binding to the polyadenylation signal sequence (AAUAAA) and interacting with other polyadenylation factors.
• CSTF-77 (CSTF3): This subunit serves as a scaffold, linking CSTF-50 and CSTF-64 and interacting with other components of the 3'-end processing machinery.

Classification and Subtypes

The CSTF complex does not have distinct subtypes but consists of different subunits that work together to achieve its function. Each subunit has specific roles and multiple isoforms that might have tissue-specific or developmental stage-specific expression patterns, adding to the regulation complexity of mRNA processing.

Function and Biological Significance

• 3'-End Processing of Pre-mRNA: CSTF is essential for the cleavage of pre-mRNA at specific sites downstream of the polyadenylation signal sequence, followed by the addition of a poly(A) tail.
• Gene Expression Regulation: By participating in the 3'-end processing, CSTF influences the stability, transport, and translation efficiency of mRNA, thereby regulating gene expression.
• Coordination with Transcription: CSTF interacts with the C-terminal domain of RNA polymerase II, coordinating transcription termination with pre-mRNA processing.
• Alternative Polyadenylation: CSTF is involved in alternative polyadenylation, a mechanism that generates diverse mRNA isoforms from a single gene, affecting mRNA localization, stability, and translation.

Clinical Issues

• Cancer: Dysregulation of CSTF components has been associated with various cancers. Aberrant polyadenylation can lead to the production of unstable or improperly regulated mRNAs, contributing to oncogenesis.
• Neurological Disorders: Mutations or altered expression of CSTF subunits can affect the processing of mRNAs involved in neural development and function, potentially leading to neurological disorders.
• Developmental Defects: Proper function of CSTF is critical during development, and its dysfunction can result in developmental abnormalities due to misregulation of gene expression.

Summary

Cleavage stimulation factor (CSTF) is a critical component of the mRNA 3'-end processing machinery, ensuring the proper cleavage and polyadenylation of pre-mRNA. The complex is composed of three main subunits, each with specific functions that contribute to recognizing and processing pre-mRNA substrates. CSTF plays a significant role in regulating gene expression by influencing mRNA stability and translation. Dysregulation of CSTF can lead to various clinical issues, including cancer and neurological disorders. Understanding the structure and function of CSTF is crucial for elucidating its role in gene expression and its implications in disease.