Genome complexity: complex telomere structure (Introduction)

by David Turell , Wednesday, April 25, 2018, 20:44 (2192 days ago) @ David Turell

An unbelievably complex enzyme protein complex makes the telomere:

https://www.nature.com/articles/d41586-018-04756-3?utm_source=breakingnews&utm_medi...

"In a paper published in Nature, Nguyen et al.4 report a structure of human telomerase bound to DNA, providing an unprecedented view of how the enzyme complex is organized and establishing a framework for drug discovery.

"Telomerase is a ribonucleoprotein (RNP) enzyme — part RNA, part protein. To retain normal function, the enzyme must contain at least a telomerase reverse transcriptase (TERT) protein subunit and a long, non-coding telomerase RNA (TR). Telomerase complexes also usually include several species-specific proteins that are important for regulating RNP assembly5. The enzyme maintains telomeres by catalysing the addition of simple DNA-sequence repeats onto the ends of linear chromosomes. The catalytic TERT subunit uses a small portion of TR as a template for these repeats.

"Vertebrate telomerases also belong to the family of box H/ACA RNP complexes, which generally modify essential cellular RNAs such as transfer RNAs, ribosomal RNA and spliceosomal RNA6. Curiously, despite possessing the RNA and protein components of H/ACA RNPs, telomerase does not exhibit the RNA-modifying activity typically associated with this class of complex.

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"The structural segregation of the catalytic core and H/ACA lobe raises the question of why the telomerase complex has retained the large H/ACA RNP throughout evolution. Part of the answer is likely to be that TCAB1 is needed to mediate trafficking of telomerase components during RNP assembly. However, another striking feature of the H/ACA lobe is that its proteins seem to promote a specific conformation of TR that brings the CR4/5 domain close to the catalytic core, where it is needed to support catalysis. This bears a remarkable resemblance to the T. thermophila telomerase RNP, in which an RNA-binding protein called p65 is required to remodel TR and promote contacts with the catalytic TERT subunit13,17. This resemblance suggests that telomerases from different organisms have co-opted different types of RNA-binding protein to promote RNP assembly. The idea that the H/ACA proteins direct RNA folding can be tested experimentally, using the new structural model as a framework with which to design and interpret incisive experiments.

"Nguyen and colleagues’ work sets a new bar for structural models of human telomerase, but there is still work to be done. A complete view of telomerase structure and function will require atomic-resolution models of the enzyme in its various functional states. Advances in cryoEM techniques, together with other structural and biophysical tools, will no doubt continue to enhance our appreciation of the intricate workings of this fascinating enzyme."

Comment: Be sure to look at the illustration of this structure. This is a giant molecule enzyme which protects chromosomes all during life as cells divide constantly. It is a vital part of living material. Not found by any chance mechanism. Must have been designed.