Related Experiment Video
Updated: Jan 7, 2026
08:53
A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
Published on: September 15, 2021
3.2K
SF3B1K700E rewires splicing of cell cycle regulators
Mai Baker1,2, Eden Engel3,4, Aveksha Sharma3
1Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel mib.sal89@gmail.com maayan.salton@mail.huji.ac.il.
RNA (New York, N.Y.)
|December 24, 2025
Summary
Mutations in SF3B1 (a spliceosome component) disrupt RNA splicing, affecting cell cycle control and promoting cancer. The SF3B1K700E mutation specifically alters splicing of G2/M regulators like ARPP19, impacting cell division and patient survival.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- Pre-mRNA splicing is vital for cellular homeostasis and tightly regulated, especially for cell cycle progression.
- SF3B1, a spliceosome component, is crucial for alternative splicing and frequently mutated in cancers.
- The SF3B1K700E mutation disrupts splicing and cell cycle control, contributing to tumorigenesis.
Purpose of the Study:
- To investigate the impact of SF3B1K700E mutation on RNA splicing patterns.
- To identify splicing alterations linked to the SF3B1K700E mutation and their functional consequences.
- To explore the relationship between SF3B1-dependent splicing, cell cycle regulation, and cancer development.
Main Methods:
- RNA sequencing (RNA-seq) of K562 erythroleukaemia cells expressing wild-type or SF3B1K700E.
- siRNA-mediated depletion of SF3B1 in HeLa cells to validate mutation-dependent splicing signatures.
- Pharmacological inhibition of DYRK1A and serine/threonine phosphatases.
- Functional assays including ectopic expression of ARPP19-long isoform.
- Analysis of TCGA-AML cohort data.
Main Results:
- Identified 763 high-confidence splicing alterations in SF3B1K700E cells, enriched for G2/M regulators (e.g., ARPP19, ENSA, STAG2, ECT2).
- Increased inclusion of ARPP19 exon 2 leads to ARPP19-long isoform, inhibiting PP2A-B55 and promoting mitosis.
- A subset of SF3B1K700E-linked splicing changes were observed upon SF3B1 depletion, indicating a mutation-specific spliceosomal signature.
- Kinase-phosphatase signaling (DYRK1A, phosphatases) influences ARPP19 exon 2 inclusion.
- Ectopic ARPP19-long expression accelerated mitotic exit; high ARPP19-long levels correlated with poorer survival in AML patients.
Conclusions:
- SF3B1K700E mutation drives specific splicing alterations impacting cell cycle regulators.
- The ARPP19-long isoform plays a role in mitotic progression and is linked to adverse outcomes in AML.
- SF3B1-dependent splicing dysregulation is a key mechanism in cancer development, offering potential therapeutic targets.
Related Concept Videos
02:37Restarting Stalled Replication Forks
6.2K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.2K
01:28The Cell Cycle Control System
5.2K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
5.2K
02:11The Cell Cycle Control System
13.8K
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
13.8K
01:23Negative Regulator Molecules
38.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.2K
02:53Conservative Site-specific Recombination and Phase Variation
6.6K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.6K
01:24Methods of Nuclear Reprogramming
2.1K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.1K