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A weak C’ box renders U3 snoRNA levels dependent on hU3-55K binding

Lookup NU author(s): Andy Knox, Dr Kenneth McKeegan, Charles Debieux, Dr Hannah Richardson, Dr Nick Watkins

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Abstract

The rate of ribosome biogenesis, which is down-regulated in terminally differentiated cells and up-regulated in most cancers, regulates growth rate and is linked to the cell’s proliferative potential. The U3 box C/D small nucleolar (sno)RNP is an integral component of the small subunit (SSU) processome and is essential for 18S ribosomal (r)RNA processing. We show that U3 snoRNP assembly, and therefore U3 snoRNA accumulation, is regulated through the U3-specific protein hU3-55K. Furthermore, we report that the levels of several SSU processome components, including the U3 snoRNA, but not other box C/D snoRNAs, are specifically down-regulated during human lung (CaCo-2) and colon (CaLu-3) epithelial cell differentiation. c-Myc is reported to play an integral role in regulating ribosome production by controlling the expression of many ribosome biogenesis factors. Our data indicate that this regulation is, however, not dependent on c-Myc as the level of this protein does not change during epithelial cell differentiation. In addition, depletion of c-Myc had only a mild affect on the levels of SSU processome proteins. CaCo-2 are colon adenocarcinoma epithelial cells that are believed to revert to their pre-cancerous state during differentiation. This suggests a significant increase in the levels of specific SSU processome components during tumourogenesis.


Publication metadata

Author(s): Knox AA, McKeegan KS, Debieux CM, Traynor A, Richardson H, Watkins NJ

Publication type: Article

Publication status: Published

Journal: Molecular and Cellular Biology

Year: 2011

Volume: 31

Issue: 12

Pages: 2404-2412

Print publication date: 19/04/2011

ISSN (print): 0270-7306

ISSN (electronic): 1098-5549

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/MCB.05067-11

DOI: 10.1128/MCB.05067-11


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Funding

Funder referenceFunder name
BB/F006853/1Biotechnology and Biological Sciences Research Council
G0501666Medical Research Council

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