Maternally Inherited Stable Intronic Sequence RNA Triggers a Self-Reinforcing Feedback Loop during Development.

Maternally inherited noncoding RNAs (ncRNAs) can regulate zygotic gene expression across generations [1-4]. Recently, many stable intronic sequence RNAs (sisRNAs), which are byproducts of pre-mRNA splicing, were found to be maternally deposited and persist till zygotic transcription in Xenopus and Drosophila [5-7]. In various organisms, sisRNAs can be in linear or circular conformations, and they have been suggested to regulate host gene expression [5-10]. It is unknown whether maternally deposited sisRNAs can regulate zygotic gene expression in the embryos. Here, we show that a maternally inherited sisRNA (sisR-4) from the deadpan locus is important for embryonic development in Drosophila. Mothers, but not fathers, mutant for sisR-4 produce embryos that fail to hatch. During embryogenesis, sisR-4 promotes transcription of its host gene (deadpan), which is essential for development. Interestingly, sisR-4 functions by activating an enhancer present in the intron where sisR-4 is encoded. We propose that a maternal sisRNA triggers expression of its host gene via a positive feedback loop during embryogenesis.

Tay ML ，Pek JW 《-》

Stable intronic sequence RNAs have possible regulatory roles in Drosophila melanogaster.

Stable intronic sequence RNAs (sisRNAs) have been found in Xenopus tropicalis, human cell lines, and Epstein-Barr virus; however, the biological significance of sisRNAs remains poorly understood. We identify sisRNAs in Drosophila melanogaster by deep sequencing, reverse transcription polymerase chain reaction, and Northern blotting. We characterize a sisRNA (sisR-1) from the regena (rga) locus and show that it can be processed from the precursor messenger RNA (pre-mRNA). We also document a cis-natural antisense transcript (ASTR) from the rga locus, which is highly expressed in early embryos. During embryogenesis, ASTR promotes robust rga pre-mRNA expression. Interestingly, sisR-1 represses ASTR, with consequential effects on rga pre-mRNA expression. Our results suggest a model in which sisR-1 modulates its host gene expression by repressing ASTR during embryogenesis. We propose that sisR-1 belongs to a class of sisRNAs with probable regulatory activities in Drosophila.

Pek JW ，Osman I ，Tay ML ，Zheng RT ... -  《-》

DIP1 modulates stem cell homeostasis in Drosophila through regulation of sisR-1.

Wong JT ，Akhbar F ，Ng AYE ，Tay ML ，Loi GJE ，Pek JW ... -  《Nature Communications》

Generation of Drosophila sisRNAs by Independent Transcription from Cognate Introns.

Although stable intronic sequence RNAs (sisRNAs) are conserved in plants and animals, their functional significance is still unclear. We identify a pool of polyadenylated maternally deposited sisRNAs in Drosophila melanogaster. These sisRNAs can be generated by independent transcription from the cognate introns. The ovary-specific poly(A) polymerase Wispy mediates the polyadenylation of maternal sisRNAs and confers their stability as maternal transcripts. A developmentally regulated sisRNA sisR-3 represses the expression of a long noncoding RNA CR44148 and is required during development. Our results expand the pool of sisRNAs and suggest that sisRNAs perform regulatory functions during development in Drosophila.

Jia Ng SS ，Zheng RT ，Osman I ，Pek JW ... -  《iScience》

Stable Intronic Sequence RNAs Engage in Feedback Loops.

Stable intronic sequence RNAs (sisRNAs) are conserved in various organisms. Recent observations in Drosophila suggest that sisRNAs often engage in regulatory feedback loops to control the expression of their parental genes. The use of sisRNAs as mediators for local feedback control may be a general phenomenon.

Pek JW 《TRENDS IN GENETICS》