Defect Transport Mechanism Leads to Shortened Chromosome Ends

Scientists at the University of Göttingen have deciphered the biogenesis of an enzyme complex whose role is to ensure that the ends of chromosomes are not shortened during the cell division process and that the genetic material is fully maintained. To be fully functional, telomerase RNA has to be shuttled in and out of the nucleus. If this process is disturbed, the enzyme complex is no longer able to do its job. The results were published in Cell Reports magazine.

Telomerase is an enzyme from the nucleus that consists of proteins and a non-coding RNA. The role of this enzyme complex is to lengthen the ends of the chromosomes (telomeres) after cell division in order to prevent a successive shortening of the genetic material (DNA) that automatically occurs when DNA is replicated. Whereas telomerase is not detectable in resting cells, it exists in growing tissue, i.e. in cells that are continuously dividing such as bone marrow cells, germline cells or embryonic stem cells as well as certain types of immune cells. It is also active in cancer cells, helping them to divide an infinite number of times and thus spread throughout the body. Unlike cancer cells, normal somatic cells undergo a finite number of cell divisions – they grow old and eventually die.

In their research at the Göttingen Center for Molecular Biosciences (GZMB) the scientists were now able to show how telomerase RNA is transported out of the nucleus into the ambient cytoplasm. There, outside the cell nucleus, it recruits proteins and matures into the large enzyme complex telomerase. Once functional, the telomerase is re-imported into the nucleus, where it attaches to the DNA and lengthens the ends of the chromosomes. "For the telomere elongation process to run smoothly, the RNA has to enter the cytoplasm and bind to the proteins it needs for the later process in the nucleus," says Professor Heike Krebber from the Molecular Genetics department at Göttingen University, who conducted the study together with her PhD students Haijia Wu and Daniel Becker. "Defects in this transport mechanism therefore lead to a successive shortening of the telomeres."

Further information: www.img.bio.uni-goettingen.de/Krebber-lab_homepage.html