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A more recent version of this article appeared on June 1, 2007
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Submitted on January 29, 2007
Revised on March 13, 2007
Accepted on March 20, 2007
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803
Monitoring Editor: A. Gregory Matera
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, while 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 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, while immuno-fluorescence 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
50% loss correlated with larval and pupal lethality, disrupted nuclear structures, and in some cases melanotic tumors, while 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 the Treacher Collins Syndrome. Similarly, overexpression of either isoform caused embryonic and larval lethality, thus indicating proper expression of Nopp140 is critical for normal development.