Question

#1: Gene Transcription and Translation

Write a brief statement hypothesizing as to why mRNA is so unstable in most bacteria (t1/2 of about 1 minute), when the same half-life is more like 1 hour in higher organisms?

Answer 1

Messenger RNA (mRNA), transcribed from a gene on a DNA template, carries information that encodes the directions for protein synthesis by ribosomes. Approximately 25,000 to 30,000 genes in the human genome are present in most of your body cells, but each cell expresses only a small fraction of them. Messenger RNA degradation is one of the methods used by cells to regulate which genes are expressed and when. Transcription is the synthesis of messenger RNA from a DNA template. The mRNA created from the process of transcription can leave the nucleus and enter the cytoplasm where it is transcribed by ribosomes to create protein products. Different messenger RNA are translated at different rates by the cell. Each mRNA differs in the rate at which they are translated into protein and in the stability of the mRNA molecule. The longer-lasting an mRNA molecule is, the more protein products that can be transcribed from the mRNA sequence.

Most bacterial mRNA have a half-life of only a few minutes with bacterial mRNA half-lives varying from less than 1 minute up to 20 minutes. The average half-life of human mRNA is 10 hours with human mRNA half-lives varying from 30 minutes - many hours.

While cells degrade messenger RNA to regulate the amount of proteins that can be translated from each mRNA molecule, they also modify mRNA molecules in a way that increases the stability of the molecule and increases the protein output under specific conditions and at certain times. The addition of a polyA tail to the 3' end of an mRNA molecule increases the stability of the mRNA molecule. The longer the polyA tail, the more stable the molecule and the more protein that can be translated.

Prokaryotic gene expression is mainly regulated on transcriptional level, which is only possible with short mRNA half-life times. Only when an RNA is unstable its accumulation depends on transcription. Eukaryotic gene expression is much more often regulated on translational level, which is only possible when the mRNAs are stable. Only stable mRNAs can be activated/deactivated by translation. If they would be unstable the regulation mode would switch back to transcriptional regulation. The concentration of any species of RNA in the cell is proportional to its rate of turnover. In general prokaryotic mRNAs have very short half-life of 2 to 5 minutes, for they don’t have protective features that are found in Eukaryote (EK) mRNAs, such as cap at 5’end and poly-A at 3’ end. In bacterial cells, as they are synthesized they are either subjected to translation. If the 5’ end fails to initiate translation, exonuclease acts upon them. Most of the mRNAs are destined to be degraded, so the half-life is very short, three to five minutes. Whereas, in eukaryotes, these mechanisms are known to function in both the nucleus and cytoplasm. Fidelity checks of mRNA molecules in the nucleus results in the degradation of improperly processed transcripts before export into the cytoplasm. Transcripts are subject to further surveillance again in cytoplasm. Cytoplasmic surveillance mechanisms assess mRNA transcripts for the absence of stop codons or presence of premature stop codons or other insurmountable knots or problems.