Related Experiment Video

Updated: May 28, 2025

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
11:34

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

Published on: August 9, 2019

6.6K

Immediate early splicing controls translation in activated T-cells and is mediated by hnRNPC2 phosphorylation

Mateusz Dróżdż1, Luíza Zuvanov1, Gopika Sasikumar2

  • 1Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Freie Universität Berlin, Takustr. 6, 14195, Berlin, Germany.

The EMBO Journal
|February 13, 2025
PubMed

Insights

Immediate early splicing (IES) is a rapid cellular response to stimuli, affecting translation machinery like ribosomal proteins and eIF5A. This process transiently reduces protein synthesis, coordinating gene expression changes during T cell activation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • Immediate early genes rapidly respond to stimuli via phosphorylation cascades, independent of new protein synthesis.
  • Cellular activation requires coordinated gene expression changes, but the mechanisms for rapid, transient regulation are not fully understood.

Purpose of the Study:

  • To identify and characterize a novel, rapid splicing mechanism termed immediate early splicing (IES).
  • To investigate the role of IES in regulating translation machinery during T cell activation.

Main Methods:

  • Investigated phosphorylation cascades targeting splicing machinery.
  • Characterized hnRNPC2-controlled IES dependent on MEK-ERK and PKCθ pathways.
  • Analyzed mRNA targets, focusing on ribosomal proteins and eIF5A.

Main Results:

  • Identified immediate early splicing (IES) as a phosphorylation-dependent splicing switch.
  • IES primarily targets mRNAs encoding translation machinery components, including eIF5A.
  • Induction of the eIF5A IES variant reduces global protein synthesis early after T cell activation.

Conclusions:

  • Immediate early splicing provides a rapid, transient mechanism to modulate translation efficiency.
  • IES plays a functional role in coordinating gene expression during T cell activation.
  • Established a new paradigm for rapid alternative splicing in cellular response pathways.
Keywords:
Immediate Early Genes (IEG)Immediate Early Splicing (IES)PKCθT Cell ActivationhnRNPC

More Related Videos

Using the E1A Minigene Tool to Study mRNA Splicing Changes10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

4.8K
A Reporter Based Cellular Assay for Monitoring Splicing Efficiency08:53

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

2.7K

Related Concept Videos

Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
20.9K
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...
6.9K
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
30.3K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.4K
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...
864