RNA editing in humans

Details

A scientist is studying post -transcriptional processing in human stem cells. He clones an unknown segment of DNA to express the gene in culture. However when he sequences the protein, he finds that one of the amino acids does not match the amino acid that would be predicted from the genetic code. After confirmations, he suspects that RNA editing has taken place. Which of the following is an example of RNA editing in humans?

A. Production of Calcitonin and Calcitonin related peptide from the same gene

B. Production of membrane bound (m Ig M) and secreted (s IgM) from the same gene

C. Increased expression of N-myc in Neuroblastoma cells

D. The production of apoprotein B48 from the transcript of apo B100 gene

E. Disappearance of globulin mRNA in response to heme.

Answer- The correct answer is- D, The production of apo B 48 from the transcript of apo B100 gene.

RNA editing changes mRNA after transcription.

RNA editing

Coding information can be changed at the mRNA level by RNA editing.

The central dogma states that for a given gene and gene product there is a linear relationship between the coding sequence in DNA, the mRNA sequence, and the protein sequence.

Changes in the DNA sequence should be reflected in a change in the mRNA sequence and, depending on codon usage, in protein sequence. However, exceptions to this dogma have been recently documented.

In RNA editing, the coding sequence of the mRNA differs from that in the cognate DNA. An example is the apolipoprotein B (apoB) gene and mRNA. In liver, the single apoB gene is transcribed into a mRNA that directs the synthesis of a 100-kDa protein, apoB100. In the intestine, the same gene directs the synthesis of the primary transcript; however, a cytidine deaminase converts a CAA codon in the mRNA to UAA at a single specific site (figure).Rather than encoding glutamine, this codon becomes a termination signal, and a 48-kDa protein (apoB48) is the result. ApoB100 and apoB48 have different functions in the two organs.

RNA editing

Figure- RNA editing of apo B100 mRNA transcript.

As regards other options-

  • Production of Calcitonin and Calcitonin related peptides from the same gene is an example of alternative splicing.
  • Production of membrane bound (m Ig M) and secreted (s IgM) from the same gene is an example of alternative poly adenylation sites. Alternative polyadenylation sites in the immunoglobulin heavy chain primary transcript result in mRNAs that are either 2700 bases long ( m) or 2400 bases long ( s). This results in a different carboxyl terminal region of the encoded proteins such that the m protein remains attached to the membrane of the B lymphocyte and the s immunoglobulin is secreted.
  • Increased expression of N-myc in Neuroblastoma cells occurs as a result of gene amplification, it is not a consequence of post transcriptional modification
  • Disappearance of globulin m RNA in response to heme results from heme’s inability to prevent phosphorylation of eIF-2(eukaryotic initiation factor-2), halting the process of protein translation. eIF-2 is one of two control points for protein synthesis initiation in eukaryotic cells. It is inactive in the phosphorylated form. eIF-2 consists of α ,β , and  γ subunits. eIF-2 is phosphorylated (on serine 51) by at least four different protein kinases (HCR, PKR, PERK, and GCN2) that are activated when a cell is under stress and when the energy expenditure required for protein synthesis would be deleterious. Such conditions include amino acid and glucose starvation, virus infection, misfolded proteins, serum deprivation, hyperosmolality, and heat shock.
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