Document Detail


RNAi knockdown of Nopp140 induces Minute-like phenotypes in Drosophila.
MedLine Citation:
PMID:  17392509     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nopp140 associates with small nucleolar RNPs to chaperone pre-rRNA processing and ribosome assembly. Alternative splicing yields two isoforms in Drosophila: Nopp140-True is homologous to vertebrate Nopp140 particularly in its carboxy terminus, whereas Nopp140-RGG contains a glycine and arginine-rich (RGG) carboxy terminus typically found in vertebrate nucleolin. Loss of ribosome function or production at critical points in development leads to Minute phenotypes in Drosophila or the Treacher Collins syndrome (TCS) in humans. To ascertain the functional significance of Nopp140 in Drosophila development, we expressed interfering RNA using the GAL4/UAS system. Reverse transcription-PCR showed variable losses of Nopp140 mRNA in larvae from separate RNAi-expressing transgenic lines, whereas immunofluorescence microscopy with isoform-specific antibodies showed losses of Nopp140 in imaginal and polyploid tissues. Phenotypic expression correlated with the percent loss of Nopp140 transcripts: a >or=50% loss correlated with larval and pupal lethality, disrupted nuclear structures, and in some cases melanotic tumors, whereas a 30% loss correlated with adult wing, leg, and tergite deformities. We consider these adult phenotypes to be Minute-like and reminiscent of human craniofacial malformations associated with TCS. Similarly, overexpression of either isoform caused embryonic and larval lethality, thus indicating proper expression of Nopp140 is critical for normal development.
Authors:
Zhengfang Cui; Patrick J DiMario
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-03-28
Journal Detail:
Title:  Molecular biology of the cell     Volume:  18     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-25     Completed Date:  2007-10-31     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2179-91     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing
Animals
Antibodies / metabolism
Congenital Abnormalities
Disease Models, Animal
Drosophila Proteins / genetics,  metabolism*
Drosophila melanogaster* / anatomy & histology,  physiology
Embryo, Nonmammalian / anatomy & histology,  metabolism
Genotype
Humans
Mandibulofacial Dysostosis
Nuclear Proteins / genetics,  metabolism*
Phenotype*
Protein Isoforms / genetics,  metabolism*
RNA Interference*
RNA, Messenger / genetics,  metabolism
RNA-Binding Proteins / genetics,  metabolism*
Recombinant Fusion Proteins / genetics,  metabolism
Syndrome
Chemical
Reg. No./Substance:
0/Antibodies; 0/Drosophila Proteins; 0/Nopp140 protein, Drosophila; 0/Nuclear Proteins; 0/Protein Isoforms; 0/RNA, Messenger; 0/RNA-Binding Proteins; 0/Recombinant Fusion Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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