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Related Concept Videos

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,...
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,...
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 stands for...
From DNA to Protein03:06

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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...
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...

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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
08:23

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Published on: February 18, 2022

Nonsense codons trigger an RNA partitioning shift.

Angela D Bhalla1, Jayanthi P Gudikote, Jun Wang

  • 1Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.

The Journal of Biological Chemistry
|December 19, 2008
PubMed
Summary
This summary is machine-generated.

Premature termination codons in TCRbeta genes trigger two responses: mRNA decay via nonsense-mediated decay (NMD) and nuclear retention (NIPS). This dual mechanism protects T-cells from harmful truncated proteins.

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Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • T-cell receptor-beta (TCRbeta) genes can acquire premature termination codons (PTCs) during gene rearrangement.
  • PTC-bearing transcripts lead to truncated proteins, which can be harmful to T-cells.

Purpose of the Study:

  • To investigate the mechanisms responsible for the down-regulation of PTC-bearing TCRbeta transcripts.
  • To elucidate the roles of nonsense-mediated decay (NMD) and nuclear retention in this process.

Main Methods:

  • Purification of cellular fractions to isolate nuclear and cytoplasmic components.
  • Analysis of mRNA kinetics following transcriptional changes.
  • RNA interference experiments to assess the function of NMD factors.
  • Identification of specific RNA sequences involved in the observed responses.

Main Results:

  • Two distinct responses collaborate to down-regulate PTC-bearing TCRbeta transcripts: rapid mRNA decay via NMD and a nuclear retention mechanism termed nonsense codon-induced partitioning shift (NIPS).
  • NMD-mediated decay appears to occur within the nucleus or at the outer nuclear membrane.
  • NIPS involves the retention of PTC-bearing transcripts in the nuclear fraction, independent of cytoplasmic NMD, and depends on NMD factors UPF1 and eIF4AIII.

Conclusions:

  • Nonsense codon-induced partitioning shift (NIPS) and nonsense-mediated decay (NMD) work together to degrade PTC-bearing transcripts within the nucleus or at the nuclear membrane.
  • This collaborative mechanism effectively prevents the production of potentially deleterious truncated T-cell receptor proteins.