What is happening in the nucleolus?

I consider this to be a very interesting place becouse:

*The WRN-helicase, the one of the few proteins that causes accelerated aging when mutated, is localised to this place. [1,2]

*In the nucleoli something very interesting seems to happen, not mentioned here before, as long as I know; With age there seems to be a loss of rDNA. How fast the loss happens is proportial to aging in the spieces, thus the loss in dogs is seven times faster than in humans. [3]

Does anyone know something more about this processes in the nucleolus? If you look in a normal textbook you will not find much information.


1. Gray MD, Wang L, Youssoufian H, Martin GM, Oshima J.
Werner helicase is localized to transcriptionally active nucleoli of cycling cells.
Exp Cell Res. 1998 Aug 1;242(2):487-94.
PMID: 9683536 [PubMed - indexed for MEDLINE]

2. Marciniak RA, Lombard DB, Johnson FB, Guarente L.
Nucleolar localization of the Werner syndrome protein in human cells.
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6887-92.
PMID: 9618508 [PubMed - indexed for MEDLINE]

3. Burkle A. Related Articles, Links
In memoriam Bernard Strehler--genomic instability in ageing: a persistent challenge.
Mech Ageing Dev. 2002 Apr 30;123(8):899-906. Review.
PMID: 12044938 [PubMed - indexed for MEDLINE]

RNA Editing which takes place before splicing, for example the activity of adenosine deaminases (ADAR1 and ADAR2), and alters splicing patterns takes place in the nucleolus.

Modulation of RNA editing by functional nucleolar sequestration of ADAR2
Christopher L. Sansam *, K. Sam Wells and Ronald B. Emeson *
http://www.pnas.org/...ll/100/24/14018

There is a correlation between the activities of the nucleolus and splicing as well as many "small nuclear associated RNAs" are localized there. I don't think it is unreasonable to tie many reasons for the disruption of function to improper editing and splicing of protein transcripts.

I would be interested in seeing how the mRNA processing and snRNA levels changed in time between various organisms as they age.

I used to work with snoRNAs (small nucleolar RNAs). These RNAs directed modifications to the bases in ribosomal RNA.

The nucleolus is where protein RNA complexes are assembled.

The major product being the assembly of ribosomes. The nucleolus is formed where the multiple copies of the ribosomal RNA are being transcribed from DNA to RNA.

Other interesting RNA protein complexes are assembled here including telomerase.

Duane

A line of investigation worth pursuit Wolfram.

As Duane said above, the nucleolus is the site of 5.8S, 18S and 28S rRNA transcription and assembly into ribosomes.

What is of interest is that the genes encoding these ribosomal components exist in high copy number in the genome in order to produce the enormous amount of ribosomes required to drive the various transcriptional functions performed in the cell.

Of relevance to aging is how the copy number influences aging rate. For instance, due to the rate of genomic erosion (DNA damage) is the copy number linked to senescence much like telomeres are?

I see now a connections between:

nucleolus, WRN, SIR2, CR and telomeres..

Leonard Guarente
Link between aging and the nucleolus
Genes and Development
Vol. 11, No. 19, pp. 2449-2455, October 1, 1997

Search Pubmed for "aging AND nucleolus" very many beautyfull articles there.