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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...
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...
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...
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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...

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ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast
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Arginyltransferase, its specificity, putative substrates, bidirectional promoter, and splicing-derived isoforms.

Rong-Gui Hu1, Christopher S Brower, Haiqing Wang

  • 1Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

The Journal of Biological Chemistry
|September 1, 2006
PubMed
Summary

The arginyltransferase (ATE1) gene produces multiple mRNA isoforms that regulate protein degradation via the N-end rule pathway. These isoforms may have distinct functions in cellular processes.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The N-end rule pathway degrades proteins with destabilizing N-terminal residues.
  • Arginylation, mediated by arginyltransferase (ATE1), is crucial for cardiovascular development, chromosome segregation, and nitric oxide signaling.

Purpose of the Study:

  • To investigate the diversity of mouse ATE1 mRNA isoforms and their functional implications.
  • To identify novel substrates of arginyltransferase.
  • To explore the regulatory mechanisms of ATE1 gene expression.

Main Methods:

  • Alternative splicing analysis to identify ATE1 mRNA isoforms.
  • Enzymatic assays using purified arginyltransferase isoforms.
  • Gene expression analysis in mouse tissues.
  • Identification of protein substrates using biochemical methods.

Main Results:

  • Mouse ATE1 gene generates at least six mRNA isoforms via alternative splicing, encoding active arginyltransferases with varying tissue expression.
  • The ATE1 promoter is bidirectional, driving expression of ATE1 and an uncharacterized gene.
  • GRP78 and protein-disulfide isomerase are identified as potential arginyltransferase substrates.
  • Different ATE1 isoforms exhibit distinct substrate arginylation activities, suggesting isoform-specific functions.

Conclusions:

  • Alternative splicing of ATE1 generates functionally distinct arginyltransferase isoforms.
  • The bidirectional nature of the ATE1 promoter adds another layer of gene regulation.
  • Novel substrates like GRP78 and protein-disulfide isomerase expand the known roles of the N-end rule pathway, potentially extending to the endoplasmic reticulum.