bantam Encodes a Developmentally Regulated microRNA that Controls Cell Proliferation and Regulates the Proapoptotic Gene hid in Drosophila

Abstract

Cell proliferation, cell death, and pattern formation are coordinated in animal development. Although many proteins that control cell proliferation and apoptosis have been identified, the means by which these effectors are linked to the patterning machinery remain poorly understood. Here, we report that the bantam gene of Drosophila encodes a 21 nucleotide microRNA that promotes tissue growth. bantam expression is temporally and spatially regulated in response to patterning cues. bantam microRNA simultaneously stimulates cell proliferation and prevents apoptosis. We identify the pro-apoptotic gene hid as a target for regulation by bantam miRNA, providing an explanation for bantam's anti-apoptotic activity.

bantam microRNA is a negative regulator of the Drosophila decapentaplegic pathway

“…Consistent with previous reports, we find that ban is spatially restricted in the wing disc [24] and showed low expression of the sensor in the wing pouch but high expression along the A/P and D/V boundaries (Figure 2A and Fig. S1B2).…”

“…The following UAS strains were used: (1) GS-ban (FBal0268610), which contains an insertion of the gene search UAS element upstream near the ban gene, allowing ban to be over expressed by Gal4 (also referred to as UAS-ban) [45], (2) UAS-omb (FBal0049358) [46], (3) UAS-EGFP (FBti0013986), a green fluorescent protein reporter, (4) UAS-Mad4ap , an activated Mad , which contains a mutation of serines into alanines at the four possible mitogen-activated protein kinase (MAPK) sites in the Mad linker region (S-H. Cho and R.W.P., unpublished results), (5) UAS-Daughters against dpp ( UAS-Dad , FBal0066214) [47]. Other fly strains used in this study include: a ban sensor (FBtp0017239), a line which contains tub-EGFP and two copies of the ban target sequence in the 3ʹUTR, and ban Δ1 FRT80B/TM6B (FBab0029992)[24], omb-lacZ (FBal0040912)[48], and brk-lacZ (FBal0097347) [49]. …”

“…ban was one of the first miRNAs studied in Drosophila and has been shown to affect cell death and growth [24,25]. Originally thought to be unique to Drosophila and related species (www.mirbase.org), it is now known that ban has conserved orthologs across phyla[26].…”

“…First identified in a gain-of-function screen for genes that affect tissue growth [25], the ban gene is expressed in a spatio-temporally restricted manner throughout development. ban miRNA stimulates cell proliferation through unknown downstream targets and inhibits apoptosis through its regulation of the pro-apoptotic gene head involution defective ( hid ) [24]. Studies of elevated ban expression in hippo mutant cells provided evidence that ban is a downstream target of the Hippo tumor-suppressor pathway [27–29].…”

Qipgene inFusarium oxysporumis required for normal hyphae morphology and virulence

“…Fungal small ribonucleic acids (RNAs) of 20–40 nucleotides (nt) are involved in RNA-silencing, which can regulate the expression of target genes and therefore are involved in a variety of biological processes, such as development, antiviral defence and the maintenance of genomic stability (Brennecke et al 2003; Sijen and Plasterk 2003; Baulcombe 2004; Lu et al 2005). Based on their RNA precursors and biogenesis mechanisms, these small RNAs can be divided into various types in fungi, including QDE-2-interacting small RNAs (qiRNAs), microRNA-like RNAs (milRNAs), Dicer-independent small interfering RNAs (disiRNAs), small interfering RNAs (siRNAs), long terminal repeat retrotransposon-siRNAs (LTR-siRNAs) and tRNA-derived RNA fragments (tRFs) (Jöchl et al 2008; Lee et al 2009; Nicolas et al 2010; Nunes et al 2011).…”