For the first time, a research group at the University of Tokyo has revealed that cells have a mechanism for counting gene copies and maintaining stable numbers.
Organisms maintain cell function by synthesizing various proteins.Therefore, a large amount of ribosome, which is responsible for protein synthesis, must be stably supplied.
Ribosomes are composed of proteins and ribosome RNA, and in order to supply a large amount of ribosome RNA, the ribosome RNA gene encoding it must be stably retained as a repeat gene of the same gene.However, because repeat genes tend to decrease, it has long been a mystery how cells keep the number of copies of the ribosome RNA gene constant.
The research group focused on the fact that the amount of Sir2 protein changes in response to the number of copies of the ribosome RNA gene.Normally, Sir2 suppresses the amplification mechanism within the repeat of the ribosome RNA gene to keep the repeat constant, but when the number of copies of the RNA gene decreases, the expression of the SIR2 gene is suppressed.
As a result of detailed analysis of this expression regulation mechanism, it was discovered that a factor called UAF has a role of counting the number of copies of the ribosome RNA gene and has a function of suppressing the amount of Sir2 as the number of copies decreases. When the amount of Sir2 decreases, the suppressed RNA gene amplification mechanism becomes “ON” and the recovery of the copy number is promoted, and when the copy number is sufficiently recovered, the suppression of the SIR2 gene is released and a sufficient amount is obtained again. The mechanism is that the number of copies is kept constant by supplying Sir2.
It is known that the number of copies of the ribosome RNA gene fluctuates due to cell aging and canceration.This result elucidates the mechanism by which cells maintain the ribosome RNA gene in a stable manner, and is expected to lead to the prevention and treatment of these in the future.
Paper information: [Molecular Cell]RNA polymerase I activators count and adjust ribosomal RNA gene copy number