Related Experiment Video

Updated: May 15, 2026

Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity
09:21

Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity

Published on: October 22, 2018

FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2

Jacob C Schwartz1, Christopher C Ebmeier, Elaine R Podell

  • 1Howard Hughes Medical Institute.

Genes & Development
|December 20, 2012
PubMed

Insights

Fused in sarcoma (FUS) protein binds RNA polymerase II CTD, preventing abnormal phosphorylation. FUS loss causes transcription issues and altered mRNA, revealing its general role in transcription regulation.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Genetics

Background:

  • Mutations in the fused in sarcoma (FUS) protein are linked to amyotrophic lateral sclerosis (ALS).
  • The precise physiological function of FUS in normal cellular processes remains unclear.
  • Understanding FUS's role is crucial for insights into ALS pathogenesis.

Purpose of the Study:

  • To elucidate the normal function of the FUS protein in gene transcription.
  • To investigate the interaction between FUS and RNA polymerase II (RNAP2).
  • To determine the consequences of FUS loss on RNAP2 activity and mRNA processing.

Main Methods:

  • Chromatin immunoprecipitation assays to detect FUS binding to RNAP2.
  • Analysis of RNAP2 C-terminal domain (CTD) phosphorylation patterns.
  • RNA sequencing to assess mRNA isoform expression and polyadenylation site usage.

Main Results:

  • FUS directly binds to the C-terminal domain (CTD) of RNA polymerase II (RNAP2).
  • FUS prevents aberrant Ser2 hyperphosphorylation of the RNAP2 CTD across numerous human genes.
  • Loss of FUS results in RNAP2 stalling at transcription start sites.
  • FUS deficiency promotes a shift in mRNA expression towards earlier polyadenylation sites.

Conclusions:

  • FUS plays a critical role in regulating RNAP2 CTD phosphorylation during transcription.
  • Beyond alternative splicing, FUS has a general function in orchestrating transcription fidelity.
  • These findings provide new insights into FUS's function and its implications in ALS.

More Related Videos

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events10:59

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events

Published on: May 13, 2019

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

Related Concept Videos

Transcription Initiation01:47

Transcription Initiation

Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...