GENETIC COMPENSATION BETWEEN RIBOSOMAL PROTEIN PARALOGS MEDIATED BY A COGNATE STABLE INTRONIC SEQUENCE RNA (sisRNA) IN DROSOPHILA

Ph.DDOCTOR OF PHILOSOPHY (FOS

Genetic compensation between ribosomal protein paralogs mediated by a cognate circular RNA

Summary: Inter-regulation between related genes, such as ribosomal protein (RP) paralogs, has been observed to be important for genetic compensation and paralog-specific functions. However, how paralogs communicate to modulate their expression levels is unknown. Here, we report a circular RNA involved in the inter-regulation between RP paralogs RpL22 and RpL22-like during Drosophila spermatogenesis. Both paralogs are mutually regulated by the circular stable intronic sequence RNA (sisRNA) circRpL22(NE,3S) produced from the RpL22 locus. RpL22 represses itself and RpL22-like. Interestingly, circRpL22 binds to RpL22 to repress RpL22-like, but not RpL22, suggesting that circRpL22 modulates RpL22’s function. circRpL22 is in turn controlled by RpL22-like, which regulates RpL22 binding to circRpL22 to indirectly modulate RpL22. This circRpL22-centric inter-regulatory circuit enables the loss of RpL22-like to be genetically compensated by RpL22 upregulation to ensure robust male germline development. Thus, our study identifies sisRNA as a possible mechanism of genetic crosstalk between paralogous genes

Germline Stem Cell Heterogeneity Supports Homeostasis in Drosophila

Summary: Adult and embryonic stem cells exhibit fluctuating gene expression; however, the biological significance of stem cell heterogeneity is not well understood. We show that, in Drosophila, female germline stem cells (GSCs) exhibit heterogeneous expression of a GSC differentiation-promoting factor Regena (Rga). The Drosophila homolog of human SON, dsn, is required to maintain GSC heterogeneity by suppressing sustained high levels of Rga. Reducing the expression of Rga in dsn mutants restores GSC heterogeneity and self-renewal. Thus, GSC heterogeneity is linked to GSC homeostasis. : Pek and colleagues report that the expression of differentiation factor Rga is heterogeneous between germline stem cells (GSCs) in the Drosophila ovaries. Dsn (human homolog of SON) represses rga transcription and promotes GSC heterogeneity, which is important for GSC homeostasis. Keywords: Drosophila, germline stem cell, Regena, homeostasis, heterogeneity, CG8273, Dsn, self-renewal, differentiatio

Maternal starvation primes progeny response to nutritional stress

10.1371/journal.pgen.1009932PLoS Genetics1711e100993