Background: Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.

The Polycomb group (PcG) genes are required for maintenance of homeotic gene repression during development. Mutations in these genes can be suppressed by mutations in genes of the SWI/SNF family. We have purified a complex, termed PRC1 (Polycomb repressive complex 1), that contains the products of the PcG genes Polycomb, Posterior sex combs, polyhomeotic, Sex combs on midleg, and several other proteins. Preincubation of PRC1 with nucleosomal arrays blocked the ability of these arrays to be remodeled by SWI/SNF. Addition of PRC1 to arrays at the same time as SWI/SNF did not block remodeling. Thus, PRC1 and SWI/SNF might compete with each other for the nucleosomal template. Several different types of repressive complexes, including deacetylases, interact with histone tails. In contrast, PRC1 was active on nucleosomal arrays formed with tailless histones.

The iab-4 noncoding RNA from the Drosophila bithorax complex is the substrate for a microRNA (miRNA). Gene conversion was used to delete the hairpin precursor of this miRNA; flies homozygous for this deletion are sterile. Surprisingly, this mutation complements with rearrangement breakpoint mutations that disrupt the iab-4 RNA but fails to complement with breaks mapping in the iab-5 through iab-7 regulatory regions. These breaks disrupt the iab-8 RNA, transcribed from the opposite strand. This iab-8 RNA also encodes a miRNA, detected on Northern blots, derived from the hairpin complementary to the iab-4 precursor hairpin. Ultrabithorax is a target of both miRNAs, although its repression is subtle in both cases. Received September 10, 2007; revised version accepted November 9, 2007. It has long been known that there are many noncoding RNAs (ncRNAs) made from the bithorax complex (BX-C) in addition to the mRNAs encoding the three homeobox transcription factors. Some of these ncRNAs have been recovered from cDNA libraries (Lipshitz et al. 1987;Cumberledge et al. 1990), and many more have been detected by in situ hybridization to RNA in embryos (Sánchez-Herrero and Akam 1989;Bae et al. 2002). It has not been possible to assign any function to these ncRNAs, although there has been speculation that they may set the state of Polycomb Response Elements (Bender and Fitzgerald 2002;Hogga and Karch 2002;Rank et al. 2002;Schmitt et al. 2005).Aravin et al. (2003) characterized a large number of microRNA (miRNA) clones prepared from Drosophila RNA at a variety of developmental stages. Two of these clones matched sequences from the BX-C, mapping to the 3Ј end of a ncRNA discovered by Cumberledge et al. (1990) (Fig. 1). This ncRNA was called the "iab-4 RNA," because it was thought to come from the iab-4 segmental domain of the BX-C, and the miRNAs were named miR-iab-4 5p (five prime) and miR-iab-4 3p (three prime). More recent mapping of segmental domains (Bender and Hudson 2000) has shown that the RNA actually lies in the iab-3 domain (regulating parasegment 8), and indeed, the ncRNA is expressed from parasegment 8 through parasegment 12 ( Fig. 1; Cumberledge et al. 1990). However, the iab-4 nomenclature is maintained here to avoid confusion with the designations in other studies. Two cDNA clones for the iab-4 RNA were described by Cumberledge et al. (1990), with alternate 3Ј poly(A) sites separated by 304 base pairs (bp). The two miRNAs come from this region between these two poly(A) sites; both are presumably derived from a 70-base hairpin RNA precursor predicted from the sequence (Fig. 2).A recent study (Ronshaugen et al. 2005) suggested that the miR-iab-4 5p miRNA might be responsible for repression of Ubx in the abdominal segments where the miRNA is expressed. The conclusion was based on experiments in which miR-iab-4 5p was expressed at high levels in tissues, including the wing and haltere discs, where miR-iab-4 5p is not normally found. However, the pattern of UBX expression in PS8, where the miRNA is expressed, is...

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