A novel hamster prion protein mRNA contains an extra exon: increased expression in scrapie

G Li1, D C Bolton

  • 1IBR/CSI Center for Developmental Neuroscience and Developmental Disabilities, Staten Island, NY 10314, USA.

Brain Research
|March 21, 1997
PubMed

Insights

Researchers identified a new exon in the hamster prion protein (PrP) gene. This exon regulates PrP gene expression, particularly in astrocytes, and its expression increases during scrapie prion disease.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Prion protein (PrP) is the primary component of prions, the infectious agents responsible for fatal neurodegenerative diseases.
  • The PrP gene structure varies across species, with hamsters and humans possessing two exons, unlike mice, cattle, and sheep which have three.

Purpose of the Study:

  • To identify and characterize the missing exon in the hamster PrP gene.
  • To investigate the role of this newly identified exon in regulating PrP gene expression in hamsters, particularly in response to prion infection.

Main Methods:

  • Gene sequencing to identify the novel hamster PrP exon.
  • Quantitative analysis of PrP mRNA variants (with and without the new exon) in different brain regions.
  • Correlation analysis between PrP mRNA expression and glial fibrillary acidic protein (GFAP) mRNA expression in response to scrapie prion inoculation.

Main Results:

  • A new exon (exon 2) was identified in the hamster PrP gene, showing significant sequence homology to mouse and other species' exon 2.
  • PrP mRNA containing the new exon (mRNA[1+2+3]) was expressed at lower levels than mRNA without the exon (mRNA[1+3]) in normal hamster brain regions.
  • Scrapie prion inoculation led to increased expression of PrP mRNA[1+2+3] in the colliculi, correlating with GFAP mRNA expression, suggesting astrocyte involvement.

Conclusions:

  • The newly identified hamster PrP exon plays a regulatory role in cellular PrP expression.
  • The mRNA variant including exon 2 (mRNA[1+2+3]) may be preferentially expressed in hamster astrocytes.
  • This finding provides insights into the molecular mechanisms of PrP regulation during prion diseases.

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...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
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...
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...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...