From Heterochromatin to Long Noncoding RNAs in Drosophila: Expanding the Arena of Gene Function and Regulation.

Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc. There has been a rapid increase in the number of identified lncRNAs, although a much larger number still remains unknown. The diversity of modes of actions and functions of the limited number of Drosophila lncRNAs, which have been examined, already reflects the profound roles of such RNAs in generating and sustaining the biological complexities of eukaryotes. Several of the known Drosophila lncRNAs originate as independent sense or antisense transcripts from promoter or intergenic, intronic, or 5'/3'-UTR regions, while many of them are independent genes that produce only lncRNAs or coding as well as noncoding RNAs. The different lncRNAs affect chromatin organization (local or large-scale pan-chromosomal), transcription, RNA processing/stability, or translation either directly through interaction with their target DNA sequences or indirectly by acting as intermediary molecules for specific regulatory proteins or may act as decoys/sinks, or storage sites for specific proteins or groups of proteins, or may provide a structural framework for the assembly of substructures in nucleus/cytoplasm. It is interesting that many of the "functions" alluded to heterochromatin in earlier cytogenetic studies appear to find correlates with the known subtle as well as far-reaching actions of the different small and long noncoding RNAs. Further studies exploiting the very rich and powerful genetic and molecular resources available for the Drosophila model are expected to unravel the mystery underlying the long reach of ncRNAs.