Transcription Factor Sfp1 Regulates mRNA Synthesis and Decay by Binding to Specific Transcripts

Core Concepts

The transcription factor Sfp1 regulates both the synthesis and cytoplasmic decay of a specific set of mRNAs by binding to them co-transcriptionally, thereby imprinting their fate.

Abstract

The content describes a novel function of the transcription factor Sfp1 in regulating both the transcription and post-transcriptional fate of a specific set of mRNAs.

Key highlights:

1. Sfp1 interacts with the Pol II subunit Rpb4 and shuttles between the nucleus and cytoplasm in a transcription-dependent manner, suggesting a role in post-transcriptional regulation.
2. Sfp1 binds to a subset of mRNAs (CRAC+ genes) co-transcriptionally, with a preference for mRNAs containing a GCTGCT motif in their 3' region.
3. The capacity of Sfp1 to bind these mRNAs is dependent on the presence of a Rap1 binding site in their promoters, indicating a link between promoter elements and mRNA fate.
4. Deletion of Sfp1 leads to decreased stability of the CRAC+ mRNAs, suggesting Sfp1 stabilizes these transcripts by slowing down their deadenylation and subsequent decay.
5. Sfp1 binds not only to the promoters but also to the gene bodies of CRAC+ genes, and this binding correlates with increased Pol II backtracking, which may facilitate Sfp1's relocation from chromatin to the nascent transcript.
6. The interplay between Sfp1's regulation of transcription elongation (via Pol II backtracking) and its stabilization of the corresponding mRNAs suggests a mechanistic link between these two processes.

Stats

"Sfp1 deletion affects the mRNA synthesis rates (SR) and abundances (RA) of the ribosomal biosynthetic (RiBi) and ribosomal (RP) genes."
"Deletion of SFP1 led to reduced stability of CRAC+ mRNAs."
"Introducing a Rap1 binding site (RapBS) to a promoter resulted in a transcript whose stability was dependent on Sfp1."
"Sfp1 binding to gene bodies correlates with the density of actively elongating RNA pol II."
"Sfp1 deletion results in higher Pol II elongation rate and suppresses the effect of TFIIS deletion on transcription."
"The backtracking index (BI) values of CRAC+ genes were higher than the average, suggesting a linkage between backtracking and Sfp1 imprinting."

Quotes

"Sfp1 can regulate transcription either by binding to promoters, like most known transcription activators, or by binding to the transcribed regions (gene bodies), probably via RNA polymerase II (Pol II)."
"Sfp1's co-transcriptional binding imprints the mRNA fate, serving as a paradigm for the cross-talk between the synthesis and decay of specific mRNAs."
"Sfp1 accompanies Pol II and regulates backtracking. The backtracked Pol II is more compatible with Sfp1's relocation to the nascent transcripts, whereupon Sfp1 accompanies these mRNAs to the cytoplasm and regulates their stability."

Key Insights Distilled From

The transcription factor Sfp1 imprints specific classes of mRNAs and links their synthesis to cytoplasmic decay

by Kelbert,,M.,... at www.biorxiv.org 09-13-2023

https://www.biorxiv.org/content/10.1101/2023.09.13.557510v2

Deeper Inquiries

How might the interplay between Sfp1's regulation of transcription elongation and its stabilization of the corresponding mRNAs be exploited for therapeutic or biotechnological applications

The interplay between Sfp1's regulation of transcription elongation and its stabilization of corresponding mRNAs presents exciting opportunities for therapeutic and biotechnological applications. By understanding how Sfp1 influences both processes, researchers can potentially develop novel strategies to modulate gene expression in a controlled manner. For example, targeting Sfp1 or its associated pathways could be explored as a way to fine-tune gene expression levels in specific cell types or under certain conditions. This could be particularly valuable in gene therapy approaches where precise control over gene expression is crucial. Additionally, insights into Sfp1's dual functions could lead to the development of new tools for gene editing, RNA stability modulation, or even the design of synthetic gene circuits for biotechnological applications. Overall, leveraging the interplay between Sfp1's transcriptional and post-transcriptional activities opens up possibilities for innovative therapeutic interventions and biotechnological advancements.

What other transcription factors, beyond Sfp1, might exhibit similar dual functions in coordinating mRNA synthesis and decay, and how could this knowledge be used to better understand gene expression regulation

Several other transcription factors may exhibit similar dual functions in coordinating mRNA synthesis and decay, providing a broader understanding of gene expression regulation. Factors like Rap1, which has been shown to regulate both mRNA synthesis and decay, could be further investigated for their potential roles in mRNA stability. Additionally, factors involved in RNA processing, such as RNA-binding proteins or splicing factors, may also play a role in coordinating transcription and mRNA decay. Understanding the mechanisms by which these factors influence both processes could enhance our knowledge of gene expression regulation and provide insights into potential therapeutic targets. By studying the interplay between transcription factors and post-transcriptional regulators, researchers can uncover new layers of gene expression control and potentially identify novel pathways for intervention in disease states or biotechnological applications.

Could the Sfp1-mediated coupling of transcription and mRNA decay play a role in cellular responses to environmental or developmental cues, and if so, what might be the physiological significance of this regulatory mechanism

The Sfp1-mediated coupling of transcription and mRNA decay likely plays a significant role in cellular responses to environmental or developmental cues. In response to changing conditions, cells may need to rapidly adjust gene expression levels to adapt to new requirements. The coordination of transcription and mRNA decay by Sfp1 could provide a mechanism for fine-tuning gene expression in a timely and efficient manner. For example, in response to stress signals or developmental cues, Sfp1 may modulate the stability of specific mRNAs to ensure a rapid and precise cellular response. This regulatory mechanism could be essential for maintaining cellular homeostasis, promoting cell survival under stress conditions, or orchestrating developmental processes. Understanding the physiological significance of Sfp1's role in coordinating transcription and mRNA decay could shed light on how cells adapt to their environment and provide insights into the molecular mechanisms underlying cellular responses to external stimuli.