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Structural elucidation of a novel mechanism for bacteriophage-based inhibition of the RNA degradosome

ABSTRACT: In all domains of life, the catalysed degradation of RNA facilitates rapid adaption to changing environmental conditions. We identified a virus-encoded protein that directly binds and inhibits the RNA degradation machinery of its bacterial host, allowing efficient accumulation of viral RNA in the infected cell. Encoded by the giant phage фKZ, KZ37/Dip associates with two RNA binding sites of the RNase E component of the Pseudomonas aeruginosa RNA degradosome. Thereby, KZ37/Dip competes with the binding of RNA substrates, resulting in effective inhibition of RNA degradation. The crystal structure of KZ37/Dip (2.2 Å) reveals an unprecedented fold for which there are no identified structural homologues. The protein forms a homo-dimer that resembles a partially opened scroll and binds RNase E through exposed acidic patches on its convex outer surface. Through the activity of KZ37/Dip, фKZ has evolved a unique mechanism to down regulate a key process of its host.

INSTRUMENT(S): LCQ Classic

ORGANISM(S): Escherichia Coli

SUBMITTER: Jean-Paul Noben

LAB HEAD: Lavigne Rob

PROVIDER: PXD003285 | Pride | 2016-07-27

REPOSITORIES: Pride

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Structural elucidation of a novel mechanism for the bacteriophage-based inhibition of the RNA degradosome.

Van den Bossche An A Hardwick Steven W SW Ceyssens Pieter-Jan PJ Hendrix Hanne H Voet Marleen M Dendooven Tom T Bandyra Katarzyna J KJ De Maeyer Marc M Aertsen Abram A Noben Jean-Paul JP Luisi Ben F BF Lavigne Rob R

eLife 20160722

In all domains of life, the catalysed degradation of RNA facilitates rapid adaptation to changing environmental conditions, while destruction of foreign RNA is an important mechanism to prevent host infection. We have identified a virus-encoded protein termed gp37/Dip, which directly binds and inhibits the RNA degradation machinery of its bacterial host. Encoded by giant phage фKZ, this protein associates with two RNA binding sites of the RNase E component of the Pseudomonas aeruginosa RNA degra ...[more]

PMID: 27447594

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Project description:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor. In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (liver, lung, ovarian, omentum and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH).

			Action	DRS
	AnVDB_RneE_NC.sf3	Other
	Band01-13RneELUZ19v.sf3	Other
	Band01-14RneEYuAv.sf3	Other
	Band01-15RneELKA1v.sf3	Other
	Band01-15RneEPEV2v.sf3	Other