Forty years of the 93D puff of Drosophila melanogaster

The 93D puff of Drosophila melanogaster became attractive in 1970 because of its singular inducibility by benzamide and has since then remained a major point of focus in my laboratory. Studies on this locus in my and several other laboratories during the past four decades have revealed that (i) this locus is developmentally active, (ii) it is a member of the heat shock gene family but selectively inducible by amides, (iii) the 93D or heat shock RNA omega (hsr omega) gene produces multiple nuclear and cytoplasmic large non-coding RNAs (hsr omega-n, hsr omega-pre-c and hsr omega-c), (iv) a variety of RNA-processing proteins, especially the hnRNPs, associate with its >10 kb nuclear (hsrw-n) transcript to form the nucleoplasmic omega speckles, (v) its genomic architecture and hnRNP-binding properties with the nuclear transcript are conserved in different species although the primary base sequence has diverged rapidly, (vi) heat shock causes the omega speckles to disappear and all the omega speckle associated proteins and the hsrw-n transcript to accumulate at the 93D locus, (vii) the hsr omega-n transcript directly or indirectly affects the localization/stability/activity of a variety of proteins including hnRNPs, Sx1, Hsp83, CBP, DIAP1, JNK-signalling members, proteasome constituents, lamin C, ISWI, HP1 and poly(ADP)-ribose polymerase and (viii) a balanced level of its transcripts is essential for the orderly relocation of various proteins, including hnRNPs, RNA pol II and HP1, to developmentally active chromosome regions during recovery from heat stress. In view of such multitudes of interactions, it appears that large non-coding RNAs like those produced by the hsr omega gene may function as hubs to coordinate multiple cellular networks and thus play important roles in maintenance of cellular homeostasis.