Pcf11Edit
Pcf11 is a conserved eukaryotic protein that plays a central role in the coordination of transcription termination with pre-mRNA 3′ end processing. In yeast, it is a core component of the Cleavage Factor IA (CFIA) complex, helping to link RNA polymerase II transcription with the downstream events of RNA maturation. In metazoans, the PCF11 family has homologs that participate in similar processes, underlining the universality of the coupling between transcription and RNA processing across eukaryotes. The protein is nuclear and functions in collaboration with other RNA processing factors and the transcription machinery to ensure that transcripts are properly cleaved and polyadenylated and that transcription terminates at the correct site. Its ability to engage both the RNA transcript and the RNA polymerase II C-terminal domain (CTD) places Pcf11 at a pivotal junction of the transcription cycle. RNA polymerase II C-terminal domain 3' end processing cleavage and polyadenylation termination of transcription
Pcf11 operates within a network of factors that couple transcription to RNA maturation and termination. In yeast, CFIA’s activity contributes to site-specific cleavage of the nascent transcript and to the recruitment of downstream processing factors, helping to define the polyadenylation signal and the subsequent addition of the poly(A) tail. Pcf11’s interactions with the CTD of RNA Pol II and with other components of the processing machinery help ensure that 3′ end formation occurs cotranscriptionally. The termination consequence is often described in the context of the torpedo model, in which exonuclease activity degrades the downstream RNA after poly(A) site cleavage and promotes Pol II release, a process in which Pcf11 is typically implicated through its connections to the processing and termination machinery. transcription termination torpedo model of transcription termination Rat1 CPSF CFIA
Function and role in transcription termination
Pcf11 functions as a key connector between transcription elongation, RNA end processing, and termination. By participating in the CFIA complex, it promotes proper cleavage at the polyadenylation signal and coordinates the recruitment of processing factors that add the poly(A) tail, all while facilitating polymerase II termination. A hallmark of Pcf11 is its engagement with the RNA Pol II CTD, particularly when the CTD is phosphorylated on Ser2 during transcription, which helps recruit Pcf11 to the transcription site. This positioning enables Pcf11 to influence both the endonucleolytic cleavage step and the subsequent disassembly of the transcription complex that leads to termination. The activity of Pcf11 is thus a cornerstone of the efficient maturation of most pre-messenger RNAs and the fidelity of gene expression in eukaryotic cells. RNA polymerase II CTD 3' end processing cleavage and polyadenylation termination of transcription
Structure and domains
Pcf11 exhibits a modular architecture that underpins its dual role in RNA processing and termination. The N-terminal region contains a CTD-interaction domain (CID) that binds to the Ser2-phosphorylated CTD of RNA Pol II, helping to shepherd Pcf11 to actively transcribed genes. The C-terminal portion harbors two zinc finger motifs that contribute to RNA binding and to interactions with other components of the CFIA/CFI complexes and processing factors. The central region tends to be less conserved and is often involved in protein–protein interactions that stabilize the assembly of CFIA and its coordination with CFII and other processing factors. This arrangement allows Pcf11 to act as a bridge between the transcription machinery and the RNA processing machinery. Structural and biochemical studies have highlighted the importance of these domains for recruitment, specificity, and function. CTD zinc finger CFIA
Interaction network
Pcf11 operates in a broad interaction network. It directly binds components of the transcription termination and RNA processing machinery, including CTD of RNA Pol II, other CFIA subunits, and downstream processing factors that recognize and act at the polyadenylation signal. Its associations with exonuclease systems, such as Rat1/XRN2, support a model in which processing and termination are tightly coordinated: after cleavage, exonuclease activity degrades the downstream transcript and promotes termination, with Pcf11 ensuring the processing steps are in place to generate a proper substrate for termination. The integration of these interactions places Pcf11 at a central hub for ensuring that transcription, RNA processing, and termination proceed in a coordinated fashion. CRISPR [Note: not a primary source; see related articles] Rat1 CPSF CFIA
Evolution, conservation, and broader context
Pcf11 is conserved across diverse eukaryotes, with metazoan homologs (often referred to simply as PCF11) performing related roles in 3′ end processing and termination. The conservation of the CID and the zinc finger–containing region across species underscores the fundamental nature of coupling transcription to RNA maturation. In higher organisms, PCF11 interacts with cleavage factors such as CPSF and other components of the 3′ end processing machinery, helping to shape the termination landscape in more complex genomes. Comparative studies across species illuminate how this module has adapted to different regulatory environments while preserving core functionality. PCF11 CPSF 3' end processing transcription termination
Controversies and debates
As with many aspects of transcription termination, models for the precise mechanistic contributions of Pcf11 and CFIA are refined through ongoing research. A central debate concerns the relative dominance of the torpedo model versus allosteric/cessation-based models of termination, and where Pcf11 fits in each scenario. Proponents of the torpedo framework emphasize the role of exonuclease activity (Rat1/XRN2) acting on the cleaved RNA downstream of the poly(A) site, with Pcf11 helping to couple processing to termination by aligning recruitment and substrate availability. Others stress allosteric changes in the transcription complex after cleavage, which together with processed RNA and associated factors lead to termination without requiring complete exonucleolytic degradation. Within this landscape, Pcf11 is viewed as a critical coordinator that can influence both processing efficiency and termination timing, with different experimental systems sometimes highlighting different aspects of its function. The evolving picture reflects the complexity of co-transcriptional regulation and the integration of multiple checkpoints that ensure accurate gene expression. torpedo model of transcription termination transcription termination 3' end processing