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Related Concept Videos

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...
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...
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...
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
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...
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...

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Related Experiment Video

Updated: May 20, 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

U1 snRNP determines mRNA length and regulates isoform expression.

Michael G Berg1, Larry N Singh, Ihab Younis

  • 1Howard Hughes Medical Institute, USA.

Cell
|July 10, 2012
PubMed
Summary

The U1 snRNP (U1) protects genes from premature termination. Moderate U1 decrease causes mRNA shortening and exon switching, impacting cell states like neuronal activation and cancer.

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10:25

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Published on: April 22, 2021

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Processing

Background:

  • U1 snRNP (U1) is crucial for splicing and preventing premature transcription termination.
  • Cleavage and polyadenylation (PCPA) at cryptic polyadenylation signals (PASs) can prematurely terminate transcripts.
  • The role of U1 in regulating PCPA at internal PASs is not fully understood.

Purpose of the Study:

  • To investigate the genome-wide impact of U1 snRNP levels on PCPA and mRNA 3' end formation.
  • To explore the functional consequences of U1-mediated regulation of PCPA in different cellular contexts.
  • To elucidate the mechanism by which U1 counteracts cotranscriptional PCPA.

Main Methods:

  • Development and application of a high-throughput sequencing strategy of differentially expressed transcripts (HIDE-seq) to map PCPA sites genome-wide.
  • Experimental manipulation of U1 snRNP levels in cell models.
  • Recapitulation of neuronal activation-associated mRNA shortening by altering U1 levels.

Main Results:

  • U1 depletion led to premature termination of most nascent transcripts within ~1 kb.
  • Moderate U1 level decreases, without inhibiting splicing, dose-dependently shifted PCPA downstream.
  • This shift resulted in mRNA 3' UTR shortening and 3' exon switching, observed in activated immune/neuronal cells, stem cells, and cancer.
  • Neuronal activation-induced mRNA shortening was mimicked by U1 decrease and reversed by U1 overexpression.
  • A novel mechanism termed 'telescripting' was proposed, where U1 association with nascent transcripts counteracts cotranscriptional PCPA.

Conclusions:

  • U1 snRNP plays a critical role in preventing premature transcription termination by PCPA at cryptic PASs.
  • Dynamic regulation of U1 levels, particularly during rapid cellular responses like neuronal activation, significantly impacts mRNA 3' end processing, leading to 3' UTR shortening and exon switching.
  • Telescripting represents a novel mechanism ensuring transcriptome integrity and regulating mRNA length by U1's cotranscriptional association with nascent transcripts.