The hsrω gene is one of the earliest known examples of long-non-coding RNA (lncRNA) genes which was suggested in early 1980s (S.C.Lakhotia & T.Mukherjee (1982) Absence of novel translation products in relation toinduced activity of the 93D puff in Drosophila melanogaster. CHROMOSOMA 85: 369-375; J.A. Lengyel, L.J. Ransom, M.L. Graham, M.L. Pardue  (1980) Transcription and metabolism of RNA from the Drosophila melanogaster heat shock puff site 93D, Chromosoma 80 237–252) to not produce any protein in spite of the very high transcriptional activity in heat shocked cells. The hsrω gene is developmentally active and is a member of the heat shock gene family in Drosophila. It is also selectively inducible by amides. This gene produces multiple nuclear and cytoplasmic large non-coding RNAs. A variety of RNA processing proteins, especially the hnRNPs, associate with its >10kb nuclear (hsrω-n) transcripts to form the nucleoplasmic omega speckles (K.V. Prasanth, T.K. Rajendra, A.K. Lal & S.C. Lakhotia (2000) Omega speckles - a novel class of nuclear speckles containing hnRNPs and associated with non-coding hsr-omega RNA in Drosophila. J. CELL SCIENCE 113: 3485-3497). The genomic architecture and hnRNP binding properties with the nuclear transcript are conserved in different species although the primary base sequence has diverged rapidly. Heat shock causes the omega speckles to disappear and all the omega speckle associated proteins and the hsrω-n transcripts to accumulate at the 93D locus. The hsrω-n transcripts directly or indirectly affect synthesis/stability/activity of variety of proteins including hnRNPs, Sxl, Hsp83, CBP, DIAP1, JNK–signalling members, proteasome constituents, lamin C, ISWI, HP1 and poly(ADP)-ribose polymerase. A balanced level of its transcripts is essential for normal development of Drosophila and for the orderly relocation of various proteins, including hnRNPs and RNA pol II to developmentally active chromosome regions during recovery from heat stress. The stress-inducible human Sat III lncRNA appear to be functional counterparts of the hsrω-n transcripts (Jolly, C. and Lakhotia, S. C. (2006) Human sat III and Drosophila hsrw transcripts: a common paradigm for nuclear regulation of RNA processing in stressed cells through sequestration of RNA processing factors. NUCLEIC ACIDS RESEARCH 34: 5508–5514)

Recent Reviews

1. S. C. Lakhotia (2011) 40 years of the 93D puff of Drosophila melanogaster. J. BIOSCIENCES, 36: 399–423
2. S. C. Lakhotia (2012) Long non-coding RNAs coordinate cellular responses to stress. WIREs RNA 3:779–796 doi: 10.1002/wrna.1135

Recent papers

1. M. Mallik & S. C. Lakhotia (2009). The developmentally active and stress-inducible non-coding hsrω gene is a novel regulator of apoptosis in Drosophila. GENETICS 183: 831-852. DOI: 10.1534/genetics.109.108571 
2. M. Mallik & S. C. Lakhotia (2011). Misexpression of the developmentally active and stress-inducible non-coding hsrω gene in Drosophila has pleiotropic consequences. J. BIOSCIENCES 36: 265-280. DOI 10.1007/s12038-011-9061-x
3. M. C. Onorati, S. Lazzaro, M. Mallik, A. M.R. Ingrassia, A. K. Singh, D. P. Chaturvedi, S. C. Lakhotia, D. F.V. Corona (2011) The ISWI chromatin remodeler organizes the hsrw ncRNA-containing omega speckle nuclear compartments. PLOS GENETICS 7: e1002096. doi:10.1371/journal.pgen.1002096
4. S. C. Lakhotia, M. Mallik, A. K. Singh & M. Ray (2012) The large non-coding hsrw-n transcripts are essential for thermotolerance and remobilization of hnRNPs, HP1 and RNA polymerase II during recovery from heat shock in Drosophila. CHROMOSOMA 121:49-70 DOI: 10.1007/s00412-011-0341-x
5. A. K. Singh & S. C. Lakhotia (2012) The hnRNP A1 homolog Hrp36 is essential for normal development, female fecundity, omega speckle formation and stress tolerance in Drosophila melanogaster. J. BIOSCIENCES 37: 659-678.

   DOI 10.1007/s12038-012-9239-x

6. A. K. Singh & S. C. Lakhotia (2015) Dynamics of hnRNPs and omega speckles in normal and heat shocked live cell nuclei of Drosophila melanogaster. CHROMOSOMA, DOI 10.1007/s00412-015-0506-0

    

Disease relevance of Hsromega

• Male sterility associated with overexpression of the noncoding hsromega gene in cyst cells of testis of Drosophila melanogaster [1]. This original assocition has subsequently been shown to be wrong in a later study which revealed that the hsrω⁰⁵²⁴¹ allele of the non-coding hsrω gene of Drosophila melanogaster is not responsible for male sterility  (Akanksha, Moushami Mallik, Roshan Fatima and S. C. Lakhotia. 2008, The hsrω⁰⁵²⁴¹ allele of the non-coding hsrω gene of Drosophila melanogaster is not responsible for male sterility as reported earlier. J. GENETICS 87: 87-90J. GENETICS 87 : 87-90  ). The male sterility was actually due to a mutation in the Dynein Intermediate Chain Gene, Dic61B (Fatima, R. (2011)Drosophila dynein intermediate chain gene, Dic61B, is required for spermatogenesis. PLoS ONE 6(12): e27822. doi:10.1371/journal.pone.0027822).
• Over-expression of hsrω gene enhances polyQ expression induced neurodegeneration in fly models (Sengupta, S. and Lakhotia, S. C., 2006, Altered expression of the noncoding hsrωgene enhances poly-Q induced neurotoxicity in Drosophila. RNA BIOLOGY 3:28-35  ) while down-regulation of hsrω-n transcripts suppresses neurodegeneration in 127Q, Huntington's, SCA1 and SCA3 fly models (Mallik, M. and Lakhotia, S. C. 2009, RNAi for the large non-coding hsrw transcripts suppresses polyglutamine pathogenesis in Drosophila models. RNA BIOLOGY 6 464-478  ; Mallik, M. and Lakhotia, S. C. 2010, Improved activities of CREB binding protein, heterogeneous nuclear ribonucleoproteins and proteasome following downregulation of noncoding hsromega transcripts help suppress poly(Q) pathogenesis in fly models. GENETICS 184: 927-945  ).

High impact information on Hsromega

• The Hrb57A protein was recruited to the 93D locus upon heat shock and thus serves as an in vivo probe for the activity of the gene in diploid cells of the embryo [2].
• Both allelic variation and expression of nuclear and cytoplasmic transcripts of Hsr-omega are closely associated with thermal phenotype in Drosophila [3].
• At 87C there is a 1.5-kb repeated sequence homologous to another heat shock RNA [4].
• Immunoprecipitation studies using the hnRNP antibodies further demonstrated a physical association of hnRNPs and hsromega transcripts [5].

Biological context of Hsromega

• The synthesis of heat-shock RNA was DNA dependent on RNA Pol II, was sensitive to rifampicin and to actinomycin D, and represented a 70-fold enrichment over random transcription of the Drosophila genome [6].
• Stability of tandem repeats in the Drosophila melanogaster Hsr-omega nuclear RNA [7].
• All the other deficiency chromosomes tested failed to puff and to incorporate 3H-uridine following a temperature shift and did not show hybridization in this region after in situ hybridization with heat shock RNA [8].
• Since the distal breakpoint of Df(3R)eR-1 is at about -45 kb upstream of the hsromega gene it is inferred that the amide response element(s) that modulate the specific transcriptional activation of the 93D puff following treatment of salivary glands with a variety of amides is/are located in the -22 kb to about -45 kb upstream interval [9].
• Our results showed that both HCH and PCP at lower concentrations evoked strong hsromega stress gene expression in the larval tissues while endosulfan did not [10].

Anatomical context of Hsromega

• It appears that the P transposon insertion in the promoter region causes a misregulated overexpression of hsromega in cyst cells, which in turn results in excessive sequestration of hnRNPs and formation of large clusters of omega speckles in these cell nuclei [1].

Associations of Hsromega with chemical compounds

• The Df(3R)eP and Df(3R)eR-1 deletions also abolished dosage compensation at the 93D locus as well as the effect of beta-alanine levels on its heat shock inducibility [9].
• The association of HSP90 with the 93D locus was strictly heat shock dependent as shown by the absence of HSP90 in puff 93D induced by either benzamide or colchicine [11].
• Although endosulfan under similar experimental condition did not induce hsromega, strong trypan blue staining indicated extensive tissue damage after 48 h of exposure [10].
• The study further suggests that -844bp upstream sequence of the gene is adequate for hsromega inducibility against HCH and PCP but not for endosulfan for which responsive elements may be searched further upstream [10].

Other interactions of Hsromega

• This heat-shock RNA has the same cap site as the embryonic transcript, while its 3' portion entirely includes the neighbouring hsp22 gene [12].
• The hsp83, hsromega and the small hsp loci are also single in the montium genomes studied here, a common feature of all Drosophila species [13].

References