Related Experiment Video

Updated: Mar 30, 2026

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
08:53

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

3.3K

Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing

Li Zhang1, Ngoc-Tung Tran1, Hairui Su1

  • 1Department of Biochemistry and Molecular Genetics, UAB Stem Cell Institute, The University of Alabama at Birmingham, Birmingham, United States.

Elife
|November 18, 2015
PubMed

Insights

Protein arginine methyltransferase 1 (PRMT1) targets RBM15 for degradation, blocking blood cell differentiation. Targeting PRMT1 may restore megakaryocyte differentiation in acute megakaryocytic leukemia.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Hematology

Background:

  • RBM15 (RNA binding motif protein 15) is crucial for cell-fate specification, particularly in blood development.
  • Aberrant megakaryocyte differentiation is a hallmark of acute megakaryocytic leukemia (AMKL).

Purpose of the Study:

  • To investigate the regulatory mechanism of RBM15 by protein arginine methyltransferase 1 (PRMT1).
  • To elucidate the role of PRMT1-mediated RBM15 regulation in megakaryocyte differentiation and AMKL.

Main Methods:

  • Demonstrated RBM15 methylation by PRMT1 at R578, leading to ubiquitylation and degradation by CNOT4.
  • Utilized AMKL cell lines to assess the impact of PRMT1 overexpression on RBM15 levels and megakaryocyte differentiation.
  • Investigated RBM15's molecular function through RNA-binding assays and analysis of its interaction with splicing factors.

Main Results:

  • PRMT1 overexpression in AMKL cells decreased RBM15 protein levels, inhibiting terminal differentiation.
  • Restoring RBM15 levels rescued megakaryocyte differentiation.
  • RBM15 binds intronic regions of key megakaryopoiesis genes (GATA1, RUNX1, TAL1, c-MPL) and recruits SF3B1 for alternative splicing.

Conclusions:

  • PRMT1 negatively regulates RBM15 protein levels, thereby controlling alternative RNA splicing and megakaryocyte differentiation.
  • Targeting PRMT1 presents a potential therapeutic strategy for restoring megakaryocyte differentiation in AMKL.
Keywords:
CNOT4PRMT1RBM15RNA metabolismarginine methylationbiochemistryhumanhuman biologymedicineubiquitylation

More Related Videos

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast07:31

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast

Published on: June 30, 2022

3.0K
Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

7.2K

Related Concept Videos

Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
8.5K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.5K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
36.2K
RNA Stability01:53

RNA Stability

12.1K
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
61.4K
RNA Splicing01:32

RNA Splicing

20.2K