Originally published as Genetics Published Articles Ahead of Print on September 7, 2009.

Genetics, Vol. 183, 831-852, November 2009, Copyright © 2009
doi:10.1534/genetics.109.108571

The Developmentally Active and Stress-Inducible Noncoding hsr{omega} Gene Is a Novel Regulator of Apoptosis in Drosophila

Moushami Mallik and Subhash C. Lakhotia1

Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221 005, India

1 Corresponding author: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221 005, India.
E-mail: lakhotia{at}bhu.ac.in

The large nucleus limited noncoding hsr{omega}-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsr{omega} transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsr{omega} transcripts suppressed JNK activation. In addition, hsr{omega}-RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. Suppression of induced cell death following depletion of hsr{omega} transcripts was abrogated when the DIAP1-RNAi transgene was coexpressed. Our results suggest that the hsr{omega} transcripts regulate cellular levels of DIAP1 via the hnRNP Hrb57A, which physically interacts with DIAP1, and any alteration in levels of the hsr{omega} transcripts in eye disc cells enhances association between these two proteins. Our studies thus reveal a novel regulatory role of the hsr{omega} noncoding RNA on the apoptotic cell death cascade through multiple paths. These observations add to the diversity of regulatory functions that the large noncoding RNAs carry out in the cells' life.