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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...
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,...
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
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...
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 addition of a...
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...

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Updated: Jul 1, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

UPF3A and UPF3B shape the transcriptome cooperatively yet oppose cell function.

Urwah Nawaz1, Emmylou Nicolas-Martinez2, Saba Montazaribarforoushi1

  • 1Adelaide Medical School, Adelaide University, Adelaide, South Australia 5005, Australia; Robinson Research Institute, Adelaide University, Adelaide, South Australia 5005, Australia.

Journal of Molecular Biology
|June 29, 2026
PubMed
Summary
This summary is machine-generated.

The nonsense mediated mRNA decay (NMD) pathway involves UPF3A and UPF3B proteins. While both regulate gene expression, they have distinct, non-redundant roles impacting cell proliferation and development.

Keywords:
NMDNonsense Mediated mRNA DecayUPF3AUPF3Bexon junction complexgene paralogmTORneurodevelopmental disorders

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cellular Processes

Background:

  • The nonsense mediated mRNA decay (NMD) pathway is crucial for gene expression regulation and organismal development.
  • UPF3A and UPF3B are core NMD proteins, with UPF3B loss being viable but UPF3A loss being embryonic lethal, suggesting complex functional relationships.

Purpose of the Study:

  • To investigate the functional relationship and potential redundancy between UPF3A and UPF3B in the NMD pathway.
  • To elucidate the distinct roles of UPF3A and UPF3B in cellular processes beyond NMD.

Main Methods:

  • Generation of L-cell lines with manipulated UPF3A and UPF3B expression levels (knockdown and overexpression).
  • RNA sequencing to analyze transcriptome-wide changes in response to UPF3A/UPF3B alterations.
  • Assessment of cell proliferation, differentiation, and neuronal growth impacts.

Main Results:

  • Significant overlap in transcriptome changes upon loss of UPF3A or UPF3B, indicating shared regulatory functions.
  • UPF3A overexpression could not rescue UPF3B loss, suggesting non-redundant roles.
  • Opposing effects on L-cell proliferation (UPF3B loss: hyper-proliferation; UPF3A loss: hypo-proliferation) and discordant mTOR signaling activation.
  • Similar opposing impacts observed in neural progenitor cells and neuronal axon growth.

Conclusions:

  • UPF3A and UPF3B cooperate to fine-tune the transcriptome via the NMD pathway.
  • Despite cooperative roles, UPF3A and UPF3B possess distinct functions that significantly impact cell proliferation, differentiation, and neuronal development.
  • The findings challenge the notion of complete functional redundancy between UPF3A and UPF3B.